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Published in: Cellular Oncology 3/2020

01-06-2020 | Insulinoma | Review

Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors

Authors: B. Mahalakshmi, Rathinasamy Baskaran, M. Shanmugavadivu, Ngoc Tuan Nguyen, Bharath Kumar Velmurugan

Published in: Cellular Oncology | Issue 3/2020

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Abstract

Background

Insulinoma-associated protein 1 (INSM1), a transcriptional regulator with a zinc-finger DNA-binding domain, has been validated as a cytoplasmic marker for neuroendocrine differentiation of tumor cells. Next to its abundant expression in the fetal pancreas, it is expressed in brain tumors, pheochromocytomas, medullary thyroid carcinomas, insulinomas and pituitary and small-cell lung carcinomas. INSM1 is not expressed in normal adult tissues and/or most non-neuroendocrine tumors. It regulates various downstream signaling pathways, including the Sonic Hedgehog, PI3K/AKT, MEK/ERK1/2, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1 and N-Myc pathways. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumors, its role in tumor development has remained unclear.

Conclusions

Here, we highlight INSMI expression, as well as its diagnostic significance and use as a therapeutic target in various neuroendocrine tumors. Targeting signaling pathways or gene expression alterations associated with INSM1 expression may be instrumental for the design of novel therapeutic strategies for neuroendocrine tumors.
Literature
1.
go back to reference E.F. Rodriguez, J.J. Fite, S. Chowsilpa, Z. Maleki, Insulinoma-associated protein 1 immunostaining on cytology specimens: an institutional experience. Hum. Pathol. 85, 128–135 (2019)PubMed E.F. Rodriguez, J.J. Fite, S. Chowsilpa, Z. Maleki, Insulinoma-associated protein 1 immunostaining on cytology specimens: an institutional experience. Hum. Pathol. 85, 128–135 (2019)PubMed
2.
go back to reference Y. Goto, M.G. Desilva, A. Toscani, B.S. Prabhakar, A.L. Notkins, M.S. Lan, A novel human insulinoma-associated cDNA, Ia-1, encodes a protein with zinc-finger DNA-binding motifs. J. Biol. Chem. 267, 15252–15257 (1992)PubMed Y. Goto, M.G. Desilva, A. Toscani, B.S. Prabhakar, A.L. Notkins, M.S. Lan, A novel human insulinoma-associated cDNA, Ia-1, encodes a protein with zinc-finger DNA-binding motifs. J. Biol. Chem. 267, 15252–15257 (1992)PubMed
3.
go back to reference W.D. Liu, H.W. Wang, M. Muguira, M.B. Breslin, M.S. Lan, INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases. Biochem. J. 397, 169–177 (2006) W.D. Liu, H.W. Wang, M. Muguira, M.B. Breslin, M.S. Lan, INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases. Biochem. J. 397, 169–177 (2006)
4.
go back to reference M.B. Breslin, M. Zhu, A.L. Notkins, M.S. Lan, Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence. Nucleic Acids Res. 30, 1038–1045 (2002)PubMedPubMedCentral M.B. Breslin, M. Zhu, A.L. Notkins, M.S. Lan, Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence. Nucleic Acids Res. 30, 1038–1045 (2002)PubMedPubMedCentral
5.
go back to reference M.S. Gierl, N. Karoulias, H. Wende, M. StrehleC, Birchmeier, The Zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells. Genes Dev. 20, 2465–2478 (2006)PubMedPubMedCentral M.S. Gierl, N. Karoulias, H. Wende, M. StrehleC, Birchmeier, The Zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells. Genes Dev. 20, 2465–2478 (2006)PubMedPubMedCentral
6.
go back to reference S.Q. Jia, A. Ivanov, D. Blasevic, T. Muller, B. Purfurst, W. Sun, W. Chen, M.N. Poy, N. Rajewsky, C. Birchmeier, Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic beta-cell function. EMBO J. 34, 1417–1433 (2015) S.Q. Jia, A. Ivanov, D. Blasevic, T. Muller, B. Purfurst, W. Sun, W. Chen, M.N. Poy, N. Rajewsky, C. Birchmeier, Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic beta-cell function. EMBO J. 34, 1417–1433 (2015)
7.
go back to reference A.B. Osipovich, Q.M. Long, E. Manduchi, R. Gangula, S.B. Hipkens, J. Schneider, T. Okubo, C.J. Stoeckert, S. Takada, M.A. Magnuson, Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3. Development 141, 2939–2949 (2014)PubMedPubMedCentral A.B. Osipovich, Q.M. Long, E. Manduchi, R. Gangula, S.B. Hipkens, J. Schneider, T. Okubo, C.J. Stoeckert, S. Takada, M.A. Magnuson, Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3. Development 141, 2939–2949 (2014)PubMedPubMedCentral
8.
go back to reference J.E. Welcker, L.R. Hernandez-Miranda, F.E. Paul, S.Q. Jia, A. Ivanov, M. SelbachC, Birchmeier, Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors. Development 140, 4947–4958 (2013)PubMed J.E. Welcker, L.R. Hernandez-Miranda, F.E. Paul, S.Q. Jia, A. Ivanov, M. SelbachC, Birchmeier, Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors. Development 140, 4947–4958 (2013)PubMed
9.
go back to reference H. Wildner, M.S. Gierl, M. Strehle, P. PlaC, Birchmeier, Insm1 (IA-1) is a crucial component of the transcriptional network that controls differentiation of the sympathoadrenal lineage. Development 135, 473–481 (2008)PubMed H. Wildner, M.S. Gierl, M. Strehle, P. PlaC, Birchmeier, Insm1 (IA-1) is a crucial component of the transcriptional network that controls differentiation of the sympathoadrenal lineage. Development 135, 473–481 (2008)PubMed
10.
go back to reference M.S. Lan, Q. Li, J. Lu, W.S. Modi, A.L. Notkins, Genomic organization, 5'-upstream sequence, and chromosomal localization of an insulinoma-associated intronless gene, IA-1. J. Biol. Chem. 269, 14170–14174 (1994)PubMed M.S. Lan, Q. Li, J. Lu, W.S. Modi, A.L. Notkins, Genomic organization, 5'-upstream sequence, and chromosomal localization of an insulinoma-associated intronless gene, IA-1. J. Biol. Chem. 269, 14170–14174 (1994)PubMed
11.
go back to reference Q. Li, A.L. Notkins, M.S. Lan, Molecular characterization of the promoter region of a neuroendocrine tumor marker, IA-1. Biochem. Biophys. Res. Commun. 236, 776–781 (1997)PubMed Q. Li, A.L. Notkins, M.S. Lan, Molecular characterization of the promoter region of a neuroendocrine tumor marker, IA-1. Biochem. Biophys. Res. Commun. 236, 776–781 (1997)PubMed
12.
go back to reference M.S. Lan, M.B. Breslin, Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation. FASEBJ 23, 2024–2033 (2009) M.S. Lan, M.B. Breslin, Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation. FASEBJ 23, 2024–2033 (2009)
13.
go back to reference N. Pedersen, M.W. Pedersen, M.S. Lan, M.B. Breslin, H.S. Poulsen, The insulinoma-associated 1: a novel promoter for targeted cancer gene therapy for small-cell lung cancer. Cancer Gene Ther. 13, 375–384 (2006)PubMed N. Pedersen, M.W. Pedersen, M.S. Lan, M.B. Breslin, H.S. Poulsen, The insulinoma-associated 1: a novel promoter for targeted cancer gene therapy for small-cell lung cancer. Cancer Gene Ther. 13, 375–384 (2006)PubMed
14.
go back to reference E. De Smaele, C. Fragomeli, E. Ferretti, M. Pelloni, A. Po, G. Canettieri, S. Coni, L. Di Marcotullio, A. Greco, M. Moretti, C. Di Rocco, S. Pazzaglia, M. Maroder, I. Screpanti, G. GianniniA, Gulino, An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma. Neoplasia 10, 89–98 (2008)PubMedPubMedCentral E. De Smaele, C. Fragomeli, E. Ferretti, M. Pelloni, A. Po, G. Canettieri, S. Coni, L. Di Marcotullio, A. Greco, M. Moretti, C. Di Rocco, S. Pazzaglia, M. Maroder, I. Screpanti, G. GianniniA, Gulino, An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma. Neoplasia 10, 89–98 (2008)PubMedPubMedCentral
15.
go back to reference M.T. Lilo, Y. Chen, R.E. LeBlanc, INSM1 is more sensitive and interpretable than conventional immunohistochemical stains used to diagnose Merkel cell carcinoma. Am. J. Surg. Pathol. 42, 1541–1548 (2018)PubMed M.T. Lilo, Y. Chen, R.E. LeBlanc, INSM1 is more sensitive and interpretable than conventional immunohistochemical stains used to diagnose Merkel cell carcinoma. Am. J. Surg. Pathol. 42, 1541–1548 (2018)PubMed
16.
go back to reference H.W. Wang, M.B. Breslin, C.C. Chen, V. Akerstrom, Q. Zhong, M.S. Lan, INSM1 promoter-driven adenoviral Herpes Simplex Virus thymidine kinase cancer gene therapy for the treatment of primitive neuroectodermal tumors. Hum. Gene Ther. 20, 1308–1318 (2009)PubMedPubMedCentral H.W. Wang, M.B. Breslin, C.C. Chen, V. Akerstrom, Q. Zhong, M.S. Lan, INSM1 promoter-driven adenoviral Herpes Simplex Virus thymidine kinase cancer gene therapy for the treatment of primitive neuroectodermal tumors. Hum. Gene Ther. 20, 1308–1318 (2009)PubMedPubMedCentral
17.
go back to reference T. Zhang, C. Chen, M.B. Breslin, K. Song, M.S. Lan, Extra-nuclear activity of INSM1 transcription factor enhances insulin receptor signaling pathway and Nkx6.1 expression through RACK1 interaction. Cell. Signal. 26, 740–747 (2014)PubMedPubMedCentral T. Zhang, C. Chen, M.B. Breslin, K. Song, M.S. Lan, Extra-nuclear activity of INSM1 transcription factor enhances insulin receptor signaling pathway and Nkx6.1 expression through RACK1 interaction. Cell. Signal. 26, 740–747 (2014)PubMedPubMedCentral
18.
go back to reference T. Zhang, W.D. Liu, N.A. Saunee, M.B. Breslin, M.S. Lan, Zinc Finger transcription factor INSM1 interrupts Cyclin D1 and CDK4 binding and induces cell cycle arrest. J. Biol. Chem. 284, 5574–5581 (2009)PubMedPubMedCentral T. Zhang, W.D. Liu, N.A. Saunee, M.B. Breslin, M.S. Lan, Zinc Finger transcription factor INSM1 interrupts Cyclin D1 and CDK4 binding and induces cell cycle arrest. J. Biol. Chem. 284, 5574–5581 (2009)PubMedPubMedCentral
19.
go back to reference M.B. Breslin, M. Zhu, M.S. Lan, NeuroD1/E47 regulates the e-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system. J. Biol. Chem. 278, 38991–38997 (2003)PubMedPubMedCentral M.B. Breslin, M. Zhu, M.S. Lan, NeuroD1/E47 regulates the e-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system. J. Biol. Chem. 278, 38991–38997 (2003)PubMedPubMedCentral
20.
go back to reference G. Mellitzer, S. Bonne, R.F. Luco, M. Van de Casteele, N. Lenne-Samuel, P. Collombat, A. Mansouri, J. Lee, M. Lan, D. Pipeleers, F.C. Nielsen, J. Ferrer, G. GradwohlH, Heimberg, IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. EMBO J. 25, 1344–1352 (2006)PubMedPubMedCentral G. Mellitzer, S. Bonne, R.F. Luco, M. Van de Casteele, N. Lenne-Samuel, P. Collombat, A. Mansouri, J. Lee, M. Lan, D. Pipeleers, F.C. Nielsen, J. Ferrer, G. GradwohlH, Heimberg, IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. EMBO J. 25, 1344–1352 (2006)PubMedPubMedCentral
21.
go back to reference M.B. Breslin, H.W. Wang, A. Pierce, R. Aucoin, M.S. Lan, Neurogenin 3 recruits CBP co-activator to facilitate histone H3/H4 acetylation in the target gene INSM1. FEBS Lett. 581, 949–954 (2007)PubMedPubMedCentral M.B. Breslin, H.W. Wang, A. Pierce, R. Aucoin, M.S. Lan, Neurogenin 3 recruits CBP co-activator to facilitate histone H3/H4 acetylation in the target gene INSM1. FEBS Lett. 581, 949–954 (2007)PubMedPubMedCentral
22.
go back to reference J.E. Welcker, L.R. Hernandez-Miranda, F.E. Paul, S. Jia, A. Ivanov, M. SelbachC, Birchmeier, Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors. Development 140, 4947–4958 (2013)PubMed J.E. Welcker, L.R. Hernandez-Miranda, F.E. Paul, S. Jia, A. Ivanov, M. SelbachC, Birchmeier, Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors. Development 140, 4947–4958 (2013)PubMed
23.
go back to reference S.Q. Jia, H. Wildner, C. Birchmeier, Insm1 controls the differentiation of pulmonary neuroendocrine cells by repressing Hes1. Dev. Biol. 408, 90–98 (2015)PubMed S.Q. Jia, H. Wildner, C. Birchmeier, Insm1 controls the differentiation of pulmonary neuroendocrine cells by repressing Hes1. Dev. Biol. 408, 90–98 (2015)PubMed
24.
go back to reference W.H. Tao, Y. Zhang, L.J. Ma, C.J. Deng, H.L. Duan, X.H. Liang, R. Liao, S.Q. Lin, T. Nie, W.Q. Chen, C.C. Wang, C. Birchmeier, S.Q. Jia, Haploinsufficiency of INSM1 impairs postnatal baseline beta-cell mass. Diabetes 67, 2615–2625 (2018)PubMed W.H. Tao, Y. Zhang, L.J. Ma, C.J. Deng, H.L. Duan, X.H. Liang, R. Liao, S.Q. Lin, T. Nie, W.Q. Chen, C.C. Wang, C. Birchmeier, S.Q. Jia, Haploinsufficiency of INSM1 impairs postnatal baseline beta-cell mass. Diabetes 67, 2615–2625 (2018)PubMed
25.
go back to reference C.C. Chen, M.B. Breslin, M.S. Lan, INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma. Oncotarget 6, 36700–36712 (2015)PubMedPubMedCentral C.C. Chen, M.B. Breslin, M.S. Lan, INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma. Oncotarget 6, 36700–36712 (2015)PubMedPubMedCentral
26.
go back to reference G. Mellitzer, S. Bonne, R.F. Luco, M. Van De Casteele, N. Lenne-Samuel, P. Collombat, A. Mansouri, J. Lee, M. Lan, D. Pipeleers, F.C. Nielsen, J. Ferrer, G. GradwohlH, Heimberg, IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. EMBO J. 25, 1344–1352 (2006)PubMedPubMedCentral G. Mellitzer, S. Bonne, R.F. Luco, M. Van De Casteele, N. Lenne-Samuel, P. Collombat, A. Mansouri, J. Lee, M. Lan, D. Pipeleers, F.C. Nielsen, J. Ferrer, G. GradwohlH, Heimberg, IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. EMBO J. 25, 1344–1352 (2006)PubMedPubMedCentral
27.
go back to reference J. Xie, T. Cai, H. Zhang, M.S. Lan, A.L. Notkins, The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the Cbl-associated protein. Genomics 80, 54–61 (2002)PubMedPubMedCentral J. Xie, T. Cai, H. Zhang, M.S. Lan, A.L. Notkins, The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the Cbl-associated protein. Genomics 80, 54–61 (2002)PubMedPubMedCentral
28.
go back to reference A. Duggan, T. Madathany, S.C. de Castro, D. Gerrelli, K. GuddatiJ, Garcia-Anoveros, Transient expression of the conserved zinc finger gene INSM1 in progenitors and nascent neurons throughout embryonic and adult neurogenesis. J. Comp. Neurol. 507, 1497–1520 (2008)PubMed A. Duggan, T. Madathany, S.C. de Castro, D. Gerrelli, K. GuddatiJ, Garcia-Anoveros, Transient expression of the conserved zinc finger gene INSM1 in progenitors and nascent neurons throughout embryonic and adult neurogenesis. J. Comp. Neurol. 507, 1497–1520 (2008)PubMed
29.
go back to reference L.M. Farkas, C. Haffner, T. Giger, P. Khaitovich, K. Nowick, C. Birchmeier, S. Paabo, W.B. Huttner, Insulinoma-associated 1 has a panneurogenic role and promotes the generation and expansion of basal progenitors in the developing mouse neocortex. Neuron 60, 40–55 (2008)PubMed L.M. Farkas, C. Haffner, T. Giger, P. Khaitovich, K. Nowick, C. Birchmeier, S. Paabo, W.B. Huttner, Insulinoma-associated 1 has a panneurogenic role and promotes the generation and expansion of basal progenitors in the developing mouse neocortex. Neuron 60, 40–55 (2008)PubMed
30.
go back to reference H. Wildner, M.S. Gierl, M. Strehle, P. Pla, C. Birchmeier, Insm1 (IA-1) is a crucial component of the transcriptional network that controls differentiation of the sympatho-adrenal lineage. Development 135, 473–481 (2008)PubMed H. Wildner, M.S. Gierl, M. Strehle, P. Pla, C. Birchmeier, Insm1 (IA-1) is a crucial component of the transcriptional network that controls differentiation of the sympatho-adrenal lineage. Development 135, 473–481 (2008)PubMed
31.
go back to reference B. Oronsky, P.C. Ma, D. Morgensztern, C.A. Carter, Nothing But NET: A review of neuroendocrine tumors and carcinomas. Neoplasia 19, 991–1002 (2017)PubMedPubMedCentral B. Oronsky, P.C. Ma, D. Morgensztern, C.A. Carter, Nothing But NET: A review of neuroendocrine tumors and carcinomas. Neoplasia 19, 991–1002 (2017)PubMedPubMedCentral
32.
go back to reference P.S. Rush, J.N. Rosenbaum, M. Roy, R.M. Baus, D.D. Bennett, R.V. Lloyd, Insulinoma-associated 1: A novel nuclear marker in Merkel cell carcinoma (cutaneous neuroendocrine carcinoma). J. Cutan. Pathol. 45, 129–135 (2018)PubMed P.S. Rush, J.N. Rosenbaum, M. Roy, R.M. Baus, D.D. Bennett, R.V. Lloyd, Insulinoma-associated 1: A novel nuclear marker in Merkel cell carcinoma (cutaneous neuroendocrine carcinoma). J. Cutan. Pathol. 45, 129–135 (2018)PubMed
33.
go back to reference Y. Takase, Y. Naito, Y. Okabe, Y. Ishida, T. Yamaguchi, H. Abe, K. Murata, T. Ito, M. Tanigawa, A. Kawahara, H. YanoJ, Akiba, Insulinoma-associated protein 1 expression in pancreatic neuroendocrine tumours in endoscopic ultrasound-guided fine-needle aspiration cytology: An analysis of 14 patients. Cytopathology 30, 194–200 (2019)PubMed Y. Takase, Y. Naito, Y. Okabe, Y. Ishida, T. Yamaguchi, H. Abe, K. Murata, T. Ito, M. Tanigawa, A. Kawahara, H. YanoJ, Akiba, Insulinoma-associated protein 1 expression in pancreatic neuroendocrine tumours in endoscopic ultrasound-guided fine-needle aspiration cytology: An analysis of 14 patients. Cytopathology 30, 194–200 (2019)PubMed
34.
go back to reference S. Mukhopadhyay, J.K. Dermawan, C.P. Lanigan, C.F. Farver, Insulinoma-associated protein 1 (INSM1) is a sensitive and highly specific marker of neuroendocrine differentiation in primary lung neoplasms: an immunohistochemical study of 345 cases, including 292 whole-tissue sections. Mod. Pathol. 32, 100–109 (2019)PubMed S. Mukhopadhyay, J.K. Dermawan, C.P. Lanigan, C.F. Farver, Insulinoma-associated protein 1 (INSM1) is a sensitive and highly specific marker of neuroendocrine differentiation in primary lung neoplasms: an immunohistochemical study of 345 cases, including 292 whole-tissue sections. Mod. Pathol. 32, 100–109 (2019)PubMed
35.
go back to reference A. Yoshida, N. Makise, S. Wakai, A. Kawai, N. Hiraoka, INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma. Mod. Pathol. 31, 744–752 (2018)PubMed A. Yoshida, N. Makise, S. Wakai, A. Kawai, N. Hiraoka, INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma. Mod. Pathol. 31, 744–752 (2018)PubMed
36.
go back to reference M. Tanigawa, M. Nakayama, T. Taira, S. Hattori, Y. Mihara, R. Kondo, H. Kusano, K. Nakamura, Y. Abe, Y. Ishida, Y. Okabe, T. Hisaka, K. Okuda, K. Fujino, T. Ito, A. Kawahara, Y. Naito, R. Yamaguchi, J. Akiba, Y. AkagiH, Yano, Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor. Med. Mol. Morphol. 51, 32–40 (2018)PubMed M. Tanigawa, M. Nakayama, T. Taira, S. Hattori, Y. Mihara, R. Kondo, H. Kusano, K. Nakamura, Y. Abe, Y. Ishida, Y. Okabe, T. Hisaka, K. Okuda, K. Fujino, T. Ito, A. Kawahara, Y. Naito, R. Yamaguchi, J. Akiba, Y. AkagiH, Yano, Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor. Med. Mol. Morphol. 51, 32–40 (2018)PubMed
37.
go back to reference L.M. Rooper, R. Sharma, Q.K. Li, P.B. Illei, W.H. Westra, INSM1 demonstrates superior performance to the individual and combined use of synaptophysin, chromogranin and CD56 for diagnosing neuroendocrine tumors of the thoracic cavity. Am. J. Surg. Pathol. 41, 1561–1569 (2017)PubMed L.M. Rooper, R. Sharma, Q.K. Li, P.B. Illei, W.H. Westra, INSM1 demonstrates superior performance to the individual and combined use of synaptophysin, chromogranin and CD56 for diagnosing neuroendocrine tumors of the thoracic cavity. Am. J. Surg. Pathol. 41, 1561–1569 (2017)PubMed
38.
go back to reference J.N. Rosenbaum, Z.Y. Guo, R.M. Baus, H. Werner, W.M. Rehrauer, R.V. Lloyd, INSM1A anovel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms. Am. J. Clin. Pathol. 144, 579–591 (2015)PubMed J.N. Rosenbaum, Z.Y. Guo, R.M. Baus, H. Werner, W.M. Rehrauer, R.V. Lloyd, INSM1A anovel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms. Am. J. Clin. Pathol. 144, 579–591 (2015)PubMed
43.
go back to reference C. Chen, A.L. Notkins, M.S. Lan, Insulinoma-associated-1: From neuroendocrine tumor marker to cancer therapeutics. Mol. Cancer Res. 17, 1597–1604 (2019)PubMed C. Chen, A.L. Notkins, M.S. Lan, Insulinoma-associated-1: From neuroendocrine tumor marker to cancer therapeutics. Mol. Cancer Res. 17, 1597–1604 (2019)PubMed
44.
go back to reference C. Chen, M.B. Breslin, M.S. Lan, INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma. Oncotarget 6, 36700–36712 (2015)PubMedPubMedCentral C. Chen, M.B. Breslin, M.S. Lan, INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma. Oncotarget 6, 36700–36712 (2015)PubMedPubMedCentral
45.
go back to reference S. Kobayashi, T. Contractor, E. Vosburgh, Y.C.N. Du, L.H. Tang, R. Clausen, C.R. Harris, Alleles of Insm1 determine whether RIP1-Tag2 mice produce insulinomas or nonfunctioning pancreatic neuroendocrine tumors. Oncogenesis 8, 1–16 (2019) S. Kobayashi, T. Contractor, E. Vosburgh, Y.C.N. Du, L.H. Tang, R. Clausen, C.R. Harris, Alleles of Insm1 determine whether RIP1-Tag2 mice produce insulinomas or nonfunctioning pancreatic neuroendocrine tumors. Oncogenesis 8, 1–16 (2019)
40.
go back to reference H. Kajiwara, K. Hirabayashi, M. Miyazawa, N. Nakamura, T. Hirasawa, T. Muramatsu, M. Mikami, M. Yasuda, R.Y. Osamura, Immunohistochemical expression of somatostatin type 2A receptor in neuroendocrine carcinoma of uterine cervix. Arch. Gynecol. Obstet. 279, 521–525 (2009)PubMed H. Kajiwara, K. Hirabayashi, M. Miyazawa, N. Nakamura, T. Hirasawa, T. Muramatsu, M. Mikami, M. Yasuda, R.Y. Osamura, Immunohistochemical expression of somatostatin type 2A receptor in neuroendocrine carcinoma of uterine cervix. Arch. Gynecol. Obstet. 279, 521–525 (2009)PubMed
46.
go back to reference M. Petrovic, Z. Bukumiric, V. Zdravkovic, S. Mitrovic, H.D. AtkinsonV, Jurisic, The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer. Med. Oncol. 31, 823 (2014)PubMed M. Petrovic, Z. Bukumiric, V. Zdravkovic, S. Mitrovic, H.D. AtkinsonV, Jurisic, The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer. Med. Oncol. 31, 823 (2014)PubMed
47.
go back to reference M.S. Lan, E.K. Russell, J. Lu, B.E. Johnson, A.L. Notkins, Ia-1, a new marker for neuroendocrine differentiation in human lung-cancer cell-lines. Cancer Res. 53, 4169–4171 (1993)PubMed M.S. Lan, E.K. Russell, J. Lu, B.E. Johnson, A.L. Notkins, Ia-1, a new marker for neuroendocrine differentiation in human lung-cancer cell-lines. Cancer Res. 53, 4169–4171 (1993)PubMed
48.
go back to reference E.F. Rodriguez, S. Chowsilpa, Z. Maleki, Insulinoma-sssociated protein 1 immunostain: A diagnostic tool for pulmonary small cell carcinoma in cytology. Acta Cytol. 62, 333–338 (2018)PubMed E.F. Rodriguez, S. Chowsilpa, Z. Maleki, Insulinoma-sssociated protein 1 immunostain: A diagnostic tool for pulmonary small cell carcinoma in cytology. Acta Cytol. 62, 333–338 (2018)PubMed
49.
go back to reference M. Wolf, R. Holle, K. Hans, P. Drings, K. Havemann, Analysis of prognostic factors in 766 patients with small-cell lung-cancer (Sclc) - the role of sex as a predictor for survival. Br. J. Cancer 63, 986–992 (1991)PubMedPubMedCentral M. Wolf, R. Holle, K. Hans, P. Drings, K. Havemann, Analysis of prognostic factors in 766 patients with small-cell lung-cancer (Sclc) - the role of sex as a predictor for survival. Br. J. Cancer 63, 986–992 (1991)PubMedPubMedCentral
39.
go back to reference C.C. Chen, M.B. Breslin, M.S. Lan, Ectopic expression of a small cell lung cancer transcription factor, INSM1 impairs alveologenesis in lung development. BMC Pulm. Med. 16, 49 (2016)PubMedPubMedCentral C.C. Chen, M.B. Breslin, M.S. Lan, Ectopic expression of a small cell lung cancer transcription factor, INSM1 impairs alveologenesis in lung development. BMC Pulm. Med. 16, 49 (2016)PubMedPubMedCentral
50.
go back to reference K. Fujino, Y. Motooka, W.A. Hassan, M.O.A. Abdalla, Y. Sato, S. Kudoh, K. Hasegawa, K. Niimori-Kita, H. Kobayashi, I. Kubota, J. Wakimoto, M. Suzuki, T. Ito, Insulinoma-associated protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer. Am. J. Pathol. 185, 3164–3177 (2015)PubMed K. Fujino, Y. Motooka, W.A. Hassan, M.O.A. Abdalla, Y. Sato, S. Kudoh, K. Hasegawa, K. Niimori-Kita, H. Kobayashi, I. Kubota, J. Wakimoto, M. Suzuki, T. Ito, Insulinoma-associated protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer. Am. J. Pathol. 185, 3164–3177 (2015)PubMed
51.
go back to reference E.E. Doxtader, S. Mukhopadhyay, Insulinoma-associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens. Cancer Cytopathol. 126, 243–252 (2018)PubMed E.E. Doxtader, S. Mukhopadhyay, Insulinoma-associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens. Cancer Cytopathol. 126, 243–252 (2018)PubMed
52.
go back to reference O. Farouk, M.A. Ebrahim, A. Senbel, Z. Emarah, W. Abozeed, M.O. Seisa, S. Mackisack, S.A. Jalil, S. Abdelhady, Breast cancer characteristics in very young Egyptian women <= 35 years. Breast Cancer Target 8, 53–58 (2016) O. Farouk, M.A. Ebrahim, A. Senbel, Z. Emarah, W. Abozeed, M.O. Seisa, S. Mackisack, S.A. Jalil, S. Abdelhady, Breast cancer characteristics in very young Egyptian women <= 35 years. Breast Cancer Target 8, 53–58 (2016)
53.
go back to reference M.J. Duffy, Serum tumor markers in breast cancer: Are they of clinical value? Clin. Chem. 52, 345–351 (2006)PubMed M.J. Duffy, Serum tumor markers in breast cancer: Are they of clinical value? Clin. Chem. 52, 345–351 (2006)PubMed
54.
go back to reference L.E. Rosen, P. Gattuso, Neuroendocrine tumors of the breast. Arch. Pathol. Lab. Med. 141, 1577–1581 (2017)PubMed L.E. Rosen, P. Gattuso, Neuroendocrine tumors of the breast. Arch. Pathol. Lab. Med. 141, 1577–1581 (2017)PubMed
55.
go back to reference K.A. Egland, J.J. Vincent, R. Strausberg, B. Lee, I. Pastan, Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins. Proc. Natl. Acad. Sci. U. S. A. 100, 1099–1104 (2003)PubMedPubMedCentral K.A. Egland, J.J. Vincent, R. Strausberg, B. Lee, I. Pastan, Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteins. Proc. Natl. Acad. Sci. U. S. A. 100, 1099–1104 (2003)PubMedPubMedCentral
56.
go back to reference N. Bretschneider, H. Brand, N. Miller, A.J. Lowery, M.J. Kerin, F. Gannon, S. Denger, Estrogen induces repression of the breast cancer and salivary gland expression gene in an estrogen receptor alpha-dependent manner. Cancer Res. 68, 106–114 (2008)PubMed N. Bretschneider, H. Brand, N. Miller, A.J. Lowery, M.J. Kerin, F. Gannon, S. Denger, Estrogen induces repression of the breast cancer and salivary gland expression gene in an estrogen receptor alpha-dependent manner. Cancer Res. 68, 106–114 (2008)PubMed
57.
go back to reference C. Gillett, P. Smith, W. Gregory, M. Richards, R. Millis, G. Peters, D. Barnes, Cyclin D1 and prognosis in human breast cancer. Int. J. Cancer 69, 92–99 (1996)PubMed C. Gillett, P. Smith, W. Gregory, M. Richards, R. Millis, G. Peters, D. Barnes, Cyclin D1 and prognosis in human breast cancer. Int. J. Cancer 69, 92–99 (1996)PubMed
58.
go back to reference B. Zengel, E. Vardar, S. Demir, A. Alacacioglu, H. Postaci, A.G. Denecli, M. Sakizli, Beta-catenin stability, frizzled and cyclin D1 proteins expression in human breast cancer and its relation with their prognosis. EJC Suppl. 7, 288–288 (2009) B. Zengel, E. Vardar, S. Demir, A. Alacacioglu, H. Postaci, A.G. Denecli, M. Sakizli, Beta-catenin stability, frizzled and cyclin D1 proteins expression in human breast cancer and its relation with their prognosis. EJC Suppl. 7, 288–288 (2009)
59.
go back to reference B. Zengel, E. Vardar, H. Postaci, S. Kececiler, A. Alacacioglu, A.G. Denecli, M. Sakizli, beta-Catenin Stability, Cyclin D1 and Frizzled proteins expression in human breast cancer and their relation with the prognosis. Turk. Klin. Tip. Bilim. 31, 350–357 (2011) B. Zengel, E. Vardar, H. Postaci, S. Kececiler, A. Alacacioglu, A.G. Denecli, M. Sakizli, beta-Catenin Stability, Cyclin D1 and Frizzled proteins expression in human breast cancer and their relation with the prognosis. Turk. Klin. Tip. Bilim. 31, 350–357 (2011)
60.
go back to reference M. Roy, D.G. Buehler, R.R. Zhang, M.L. Schwalbe, R.M. Baus, M.S. Salamat, R.V. Lloyd, J.N. Rosenbaum, Expression of insulinoma-associated protein 1 (INSM1) and orthopedia homeobox (OTP) in tumors with neuroendocrine differentiation at rare sites. Endocr. Pathol. 30, 35–42 (2019)PubMed M. Roy, D.G. Buehler, R.R. Zhang, M.L. Schwalbe, R.M. Baus, M.S. Salamat, R.V. Lloyd, J.N. Rosenbaum, Expression of insulinoma-associated protein 1 (INSM1) and orthopedia homeobox (OTP) in tumors with neuroendocrine differentiation at rare sites. Endocr. Pathol. 30, 35–42 (2019)PubMed
61.
go back to reference R. Nadal, M. Schweizer, O.N. Kryvenko, J.I. Epstein, M.A. Eisenberger, Small cell carcinoma of the prostate. Nat. Rev. Urol. 11, 213–219 (2014)PubMedPubMedCentral R. Nadal, M. Schweizer, O.N. Kryvenko, J.I. Epstein, M.A. Eisenberger, Small cell carcinoma of the prostate. Nat. Rev. Urol. 11, 213–219 (2014)PubMedPubMedCentral
62.
go back to reference W. Wang, J.I. Epstein, Small cell carcinoma of the prostate - A morphologic and immunohistochemical study of 95 cases. Am. J. Surg. Pathol. 32, 65–71 (2008)PubMed W. Wang, J.I. Epstein, Small cell carcinoma of the prostate - A morphologic and immunohistochemical study of 95 cases. Am. J. Surg. Pathol. 32, 65–71 (2008)PubMed
63.
go back to reference Z.X. Xin, Y. Zhang, Z. Jiang, L. Zhao, L.C. Fan, Y.Q. Wang, S.W. Xie, S.G. Xun, Y.J. Zhu, J.H. Pan, Q. Liu, Y.R. Huang, B.J. Dong, W. Xue, Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate. Hum. Pathol. 79, 151–159 (2018)PubMed Z.X. Xin, Y. Zhang, Z. Jiang, L. Zhao, L.C. Fan, Y.Q. Wang, S.W. Xie, S.G. Xun, Y.J. Zhu, J.H. Pan, Q. Liu, Y.R. Huang, B.J. Dong, W. Xue, Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate. Hum. Pathol. 79, 151–159 (2018)PubMed
64.
go back to reference S. Uccella, G. Ottini, C. Facco, R. Maragliano, S. Asioli, F. Sessa, S. La Rosa, Neuroendocrine neoplasms of the head and neck and olfactory neuroblastoma. Diagnosis and classification. Pathologica 109, 14–30 (2017)PubMed S. Uccella, G. Ottini, C. Facco, R. Maragliano, S. Asioli, F. Sessa, S. La Rosa, Neuroendocrine neoplasms of the head and neck and olfactory neuroblastoma. Diagnosis and classification. Pathologica 109, 14–30 (2017)PubMed
65.
go back to reference C.B. Tempfer, I. Tischoff, A. Dogan, Z. Hilal, B. Schultheis, P. Kern, G.A. Rezniczek, Neuroendocrine carcinoma of the cervix: a systematic review of the literature. BMC Cancer 18, 530 (2018)PubMedPubMedCentral C.B. Tempfer, I. Tischoff, A. Dogan, Z. Hilal, B. Schultheis, P. Kern, G.A. Rezniczek, Neuroendocrine carcinoma of the cervix: a systematic review of the literature. BMC Cancer 18, 530 (2018)PubMedPubMedCentral
41.
go back to reference S. Kuji, R. Watanabe, Y. Sato, T. Iwata, Y. Hirashima, M. Takekuma, I. Ito, M. Abe, R. Nagashio, K. Omae, D. Aoki, T. Kameya, A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases. Gynecol. Oncol. 144, 384–390 (2017)PubMed S. Kuji, R. Watanabe, Y. Sato, T. Iwata, Y. Hirashima, M. Takekuma, I. Ito, M. Abe, R. Nagashio, K. Omae, D. Aoki, T. Kameya, A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases. Gynecol. Oncol. 144, 384–390 (2017)PubMed
66.
go back to reference K. Kriegsmann, C. Zgorzelski, D. Kazdal, M. Cremer, T. Muley, H. Winter, R. Longuespee, J. Kriegsmann, A. Warth, M. Kriegsmann, Insulinoma-associated protein 1 (INSM1) in thoracic tumors is less sensitive but more specific compared with synaptophysin, chromogranin A, and CD56. Appl. Immunohistochem. Mol. Morphol. 32, 100–109 (2018) K. Kriegsmann, C. Zgorzelski, D. Kazdal, M. Cremer, T. Muley, H. Winter, R. Longuespee, J. Kriegsmann, A. Warth, M. Kriegsmann, Insulinoma-associated protein 1 (INSM1) in thoracic tumors is less sensitive but more specific compared with synaptophysin, chromogranin A, and CD56. Appl. Immunohistochem. Mol. Morphol. 32, 100–109 (2018)
67.
go back to reference M. Svajdler, R. Mezencev, B. Saskova, O. Ondic, P. Mukensnabl, M. Michal, Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens. Hum. Pathol. 85, 58–64 (2019)PubMed M. Svajdler, R. Mezencev, B. Saskova, O. Ondic, P. Mukensnabl, M. Michal, Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens. Hum. Pathol. 85, 58–64 (2019)PubMed
68.
go back to reference C. Leblebii, B.B. Sigirci, C.K. Talu, S.B. Koca, G.E. Huq, CD10, TDAG51, CK20, AR, INSM1, and Nestin expression in the differential diagnosis of trichoblastoma and basal cell carcinoma. Int. J. Surg. Pathol. 27, 19–27 (2019) C. Leblebii, B.B. Sigirci, C.K. Talu, S.B. Koca, G.E. Huq, CD10, TDAG51, CK20, AR, INSM1, and Nestin expression in the differential diagnosis of trichoblastoma and basal cell carcinoma. Int. J. Surg. Pathol. 27, 19–27 (2019)
42.
go back to reference A.W.S. Tseng, C.C. Chen, M.B. Breslin, M.S. Lan, Tumor-specific promoter-driven adenoviral therapy for insulinoma. Cell. Oncol. 39, 279–286 (2016) A.W.S. Tseng, C.C. Chen, M.B. Breslin, M.S. Lan, Tumor-specific promoter-driven adenoviral therapy for insulinoma. Cell. Oncol. 39, 279–286 (2016)
69.
go back to reference V. Akerstrom, C. Chen, M.S. Lan, M.B. Breslin, Modifications to the INSM1 promoter to preserve specificity and activity for use in adenoviral gene therapy of neuroendocrine carcinomas. Cancer Gene Ther. 19, 828–838 (2012)PubMed V. Akerstrom, C. Chen, M.S. Lan, M.B. Breslin, Modifications to the INSM1 promoter to preserve specificity and activity for use in adenoviral gene therapy of neuroendocrine carcinomas. Cancer Gene Ther. 19, 828–838 (2012)PubMed
70.
go back to reference S.R. Michaelsen, C.L. Christensen, M. Sehested, F. Cramer, T.T. Poulsen, A.V. Patterson, H.S. Poulsen, Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells. J. Gene Med. 14, 445–458 (2012)PubMed S.R. Michaelsen, C.L. Christensen, M. Sehested, F. Cramer, T.T. Poulsen, A.V. Patterson, H.S. Poulsen, Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells. J. Gene Med. 14, 445–458 (2012)PubMed
71.
go back to reference F. Cramer, C.L. Christensen, T.T. Poulsen, M.A. Badding, D.A. Dean, H.S. Poulsen, Insertion of a nuclear factor kappa B DNA nuclear-targeting sequence potentiates suicide gene therapy efficacy in lung cancer cell lines. Cancer Gene Ther. 19, 675–683 (2012)PubMed F. Cramer, C.L. Christensen, T.T. Poulsen, M.A. Badding, D.A. Dean, H.S. Poulsen, Insertion of a nuclear factor kappa B DNA nuclear-targeting sequence potentiates suicide gene therapy efficacy in lung cancer cell lines. Cancer Gene Ther. 19, 675–683 (2012)PubMed
73.
go back to reference C.C. Chen, M.B. Breslin, M.S. Lan, Sonic hedgehog signaling pathway promotes INSM1 transcription factor in neuroendocrine lung cancer. Cell. Signal. 46, 83–91 (2018)PubMed C.C. Chen, M.B. Breslin, M.S. Lan, Sonic hedgehog signaling pathway promotes INSM1 transcription factor in neuroendocrine lung cancer. Cell. Signal. 46, 83–91 (2018)PubMed
74.
go back to reference C.C. Chen, M.B. Breslin, J.J. Guidry, M.S. Lan, 5-Iodotubercidin represses insulinoma-associated-1 expression, decreases cAMP levels, and suppresses human neuroblastoma cell growth. J. Biol. Chem. 294, 5456–5465 (2019)PubMedPubMedCentral C.C. Chen, M.B. Breslin, J.J. Guidry, M.S. Lan, 5-Iodotubercidin represses insulinoma-associated-1 expression, decreases cAMP levels, and suppresses human neuroblastoma cell growth. J. Biol. Chem. 294, 5456–5465 (2019)PubMedPubMedCentral
Metadata
Title
Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors
Authors
B. Mahalakshmi
Rathinasamy Baskaran
M. Shanmugavadivu
Ngoc Tuan Nguyen
Bharath Kumar Velmurugan
Publication date
01-06-2020
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 3/2020
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-020-00505-9

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