Skip to main content
Top
Published in: Journal of Gastrointestinal Cancer 4/2014

01-12-2014 | Original Research

HES1 as an Independent Prognostic Marker in Esophageal Squamous Cell Carcinoma

Authors: Shaghayegh Taleb, Mohammad Reza Abbaszadegan, Meysam Moghbeli, Nasim Hayati Roudbari, Mohammad Mahdi Forghanifard

Published in: Journal of Gastrointestinal Cancer | Issue 4/2014

Login to get access

Abstract

Background

Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, and its deregulation may lead to tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and recruits MAML1 as coactivator triggering the activation of notch signaling transcription complex. Hairy enhance of split-1 (HES1) is one of the notch signaling target genes which is a basic helix-loop-helix (bHLH) transcription factor acting as a proliferation stimulator through the suppression of cell cycle inhibitors such as p27 and p21.

Aims

In this study, we aimed to analyze the role of HES1 in the progression of esophageal squamous cell carcinoma (ESCC).

Methods

Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin normal samples were assessed in 50 ESCC patients by real-time polymerase chain reaction (RT-PCR).

Results

Thirteen out of 50 cases (26 %) had HES1 underexpression, while HES1 overexpression was observed only in 4 (8 %) samples. HES1 underexpression was significantly correlated with tumor depth of invasion (P = 0.035).

Conclusion

Although we have not observed any significant correlation between the HES1 expression and notch activation in ESCC, this study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC.
Literature
1.
go back to reference Forghanifard MM, Gholamin M, Farshchian M, Moaven O, Memar B, Forghani MN, et al. Cancer-testis gene expression profiling in esophageal squamous cell carcinoma: identification of specific tumor marker and potential targets for immunotherapy. Cancer Biol Ther. 2011;12(3):191–7.PubMedCrossRef Forghanifard MM, Gholamin M, Farshchian M, Moaven O, Memar B, Forghani MN, et al. Cancer-testis gene expression profiling in esophageal squamous cell carcinoma: identification of specific tumor marker and potential targets for immunotherapy. Cancer Biol Ther. 2011;12(3):191–7.PubMedCrossRef
2.
go back to reference Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol. 2009;20(3):556–63.PubMedCrossRef Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol. 2009;20(3):556–63.PubMedCrossRef
3.
go back to reference Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059–87.PubMedCrossRef Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059–87.PubMedCrossRef
5.
go back to reference Nickoloff BJ, Osborne BA, Miele L. Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene. 2003;22(42):6598–608.PubMedCrossRef Nickoloff BJ, Osborne BA, Miele L. Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene. 2003;22(42):6598–608.PubMedCrossRef
7.
go back to reference Miele L, Miao H, Nickoloff BJ. NOTCH signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets. 2006;6(4):313–23.PubMedCrossRef Miele L, Miao H, Nickoloff BJ. NOTCH signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets. 2006;6(4):313–23.PubMedCrossRef
8.
go back to reference Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of Notch signaling in cancer. Oncogene. 2008;27(38):5124–31.PubMedCrossRef Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. Rational targeting of Notch signaling in cancer. Oncogene. 2008;27(38):5124–31.PubMedCrossRef
9.
go back to reference Barolo S, Stone T, Bang AG, Posakony JW. Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless. Genes Dev. 2002;16(15):1964–76.PubMedCentralPubMedCrossRef Barolo S, Stone T, Bang AG, Posakony JW. Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless. Genes Dev. 2002;16(15):1964–76.PubMedCentralPubMedCrossRef
10.
go back to reference Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, et al. SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J. 2002;21(20):5417–26.PubMedCentralPubMedCrossRef Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, et al. SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J. 2002;21(20):5417–26.PubMedCentralPubMedCrossRef
11.
go back to reference Nakamura T, Tsuchiya K, Watanabe M. Crosstalk between Wnt and Notch signaling in intestinal epithelial cell fate decision. J Gastroenterol. 2007;42(9):705–10.PubMedCrossRef Nakamura T, Tsuchiya K, Watanabe M. Crosstalk between Wnt and Notch signaling in intestinal epithelial cell fate decision. J Gastroenterol. 2007;42(9):705–10.PubMedCrossRef
12.
go back to reference Osipo C, Golde TE, Osborne BA, Miele LA. Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Lab Invest. 2008;88(1):11–7.PubMedCrossRef Osipo C, Golde TE, Osborne BA, Miele LA. Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Lab Invest. 2008;88(1):11–7.PubMedCrossRef
13.
go back to reference Moghbeli M, Moghbeli F, Forghanifard MM, Garayali A, Abbaszadegan MR. Cancer stem cell markers in esophageal cancer. Am J Cancer Sci. 2013;2(1):37–50. Moghbeli M, Moghbeli F, Forghanifard MM, Garayali A, Abbaszadegan MR. Cancer stem cell markers in esophageal cancer. Am J Cancer Sci. 2013;2(1):37–50.
14.
go back to reference Wang Z, Li Y, Kong D, Ahmad A, Banerjee S, Sarkar FH. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression. Cancer Lett. 2010;292(2):141–8.PubMedCentralPubMedCrossRef Wang Z, Li Y, Kong D, Ahmad A, Banerjee S, Sarkar FH. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression. Cancer Lett. 2010;292(2):141–8.PubMedCentralPubMedCrossRef
17.
go back to reference Ma J, Xia J, Miele L, Sarkar FH, Wang Z. Notch signaling pathway in pancreatic cancer progression. Pancreat Disord Ther. 2013;3(114). Ma J, Xia J, Miele L, Sarkar FH, Wang Z. Notch signaling pathway in pancreatic cancer progression. Pancreat Disord Ther. 2013;3(114).
18.
go back to reference Roma J, Almazan-Moga A, Sanchez de Toledo J, Gallego S. Notch, Wnt, and hedgehog pathways in rhabdomyosarcoma: from single pathways to an integrated network. Sarcoma. 2012;2012:695603.PubMedCentralPubMedCrossRef Roma J, Almazan-Moga A, Sanchez de Toledo J, Gallego S. Notch, Wnt, and hedgehog pathways in rhabdomyosarcoma: from single pathways to an integrated network. Sarcoma. 2012;2012:695603.PubMedCentralPubMedCrossRef
19.
go back to reference Wang X, Fu Y, Chen X, Ye J, Lu B, Ye F, et al. The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol. 2010;136(7):989–96.PubMedCentralPubMedCrossRef Wang X, Fu Y, Chen X, Ye J, Lu B, Ye F, et al. The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol. 2010;136(7):989–96.PubMedCentralPubMedCrossRef
20.
go back to reference Wittekind C. 2010 TNM system: on the 7th edition of TNM classification of malignant tumors. Pathologe. 2010;31(5):331–2.PubMedCrossRef Wittekind C. 2010 TNM system: on the 7th edition of TNM classification of malignant tumors. Pathologe. 2010;31(5):331–2.PubMedCrossRef
21.
go back to reference Moghbeli M, Abbaszadegan MR, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, et al. Association of PYGO2 and EGFR in esophageal squamous cell carcinoma. Med Oncol. 2013;30(2):516.PubMedCrossRef Moghbeli M, Abbaszadegan MR, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, et al. Association of PYGO2 and EGFR in esophageal squamous cell carcinoma. Med Oncol. 2013;30(2):516.PubMedCrossRef
22.
go back to reference Rubie C, Kempf K, Hans J, Su T, Tilton B, Georg T, et al. Housekeeping gene variability in normal and cancerous colorectal, pancreatic, esophageal, gastric and hepatic tissues. Mol Cell Probes. 2005;19(2):101–9.PubMedCrossRef Rubie C, Kempf K, Hans J, Su T, Tilton B, Georg T, et al. Housekeeping gene variability in normal and cancerous colorectal, pancreatic, esophageal, gastric and hepatic tissues. Mol Cell Probes. 2005;19(2):101–9.PubMedCrossRef
23.
go back to reference Moghbeli M, Forghanifard MM, Aarabi A, Mansourian A, Abbaszadegan MR. Clinicopathological sex-related relevance of Musashi1 mRNA expression in esophageal squamous cell carcinoma patients. Pathol Oncol Res. 2014;20(2):427–33. Moghbeli M, Forghanifard MM, Aarabi A, Mansourian A, Abbaszadegan MR. Clinicopathological sex-related relevance of Musashi1 mRNA expression in esophageal squamous cell carcinoma patients. Pathol Oncol Res. 2014;20(2):427–33.
24.
go back to reference Edmunds RC, McIntyre JK, Luckenbach JA, Baldwin DH, Incardona JP. Toward enhanced MIQE compliance: reference residual normalization of qPCR gene expression data. J Biomol Tech. 2014;25(2):54–60.PubMedCentralPubMed Edmunds RC, McIntyre JK, Luckenbach JA, Baldwin DH, Incardona JP. Toward enhanced MIQE compliance: reference residual normalization of qPCR gene expression data. J Biomol Tech. 2014;25(2):54–60.PubMedCentralPubMed
25.
go back to reference Politi K, Feirt N, Kitajewski J. Notch in mammary gland development and breast cancer. Semin Cancer Biol. 2004;14(5):341–7.PubMedCrossRef Politi K, Feirt N, Kitajewski J. Notch in mammary gland development and breast cancer. Semin Cancer Biol. 2004;14(5):341–7.PubMedCrossRef
26.
go back to reference Lee JB, Werbowetski-Ogilvie TE, Lee JH, McIntyre BA, Schnerch A, Hong SH, et al. Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells. Blood. 2013;122(7):1162–73.PubMedCrossRef Lee JB, Werbowetski-Ogilvie TE, Lee JH, McIntyre BA, Schnerch A, Hong SH, et al. Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells. Blood. 2013;122(7):1162–73.PubMedCrossRef
27.
go back to reference Axelson H. The Notch signaling cascade in neuroblastoma: role of the basic helix-loop-helix proteins HASH-1 and HES-1. Cancer Lett. 2004;204(2):171–8.PubMedCrossRef Axelson H. The Notch signaling cascade in neuroblastoma: role of the basic helix-loop-helix proteins HASH-1 and HES-1. Cancer Lett. 2004;204(2):171–8.PubMedCrossRef
28.
go back to reference Miyazaki M, Kawamoto H, Kato Y, Itoi M, Miyazaki K, Masuda K, et al. Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway. J Immunol. 2005;174(5):2507–16.PubMedCrossRef Miyazaki M, Kawamoto H, Kato Y, Itoi M, Miyazaki K, Masuda K, et al. Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway. J Immunol. 2005;174(5):2507–16.PubMedCrossRef
29.
go back to reference Ross DA, Hannenhalli S, Tobias JW, Cooch N, Shiekhattar R, Kadesch T. Functional analysis of Hes-1 in preadipocytes. Mol Endocrinol. 2006;20(3):698–705.PubMedCrossRef Ross DA, Hannenhalli S, Tobias JW, Cooch N, Shiekhattar R, Kadesch T. Functional analysis of Hes-1 in preadipocytes. Mol Endocrinol. 2006;20(3):698–705.PubMedCrossRef
31.
go back to reference Liu J, Ye F, Chen H, Lu W, Zhou C, Xie X. Expression of differentiation associated protein Hes1 and Hes5 in cervical squamous carcinoma and its precursors. Int J Gynecol Cancer. 2007;17(6):1293–9.PubMedCrossRef Liu J, Ye F, Chen H, Lu W, Zhou C, Xie X. Expression of differentiation associated protein Hes1 and Hes5 in cervical squamous carcinoma and its precursors. Int J Gynecol Cancer. 2007;17(6):1293–9.PubMedCrossRef
32.
go back to reference Weng AP, Aster JC. Multiple niches for Notch in cancer: context is everything. Curr Opin Genet Dev. 2004;14(1):48–54.PubMedCrossRef Weng AP, Aster JC. Multiple niches for Notch in cancer: context is everything. Curr Opin Genet Dev. 2004;14(1):48–54.PubMedCrossRef
33.
34.
go back to reference Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood. 2006;107(6):2223–33.PubMedCrossRef Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood. 2006;107(6):2223–33.PubMedCrossRef
35.
go back to reference Nam Y, Aster JC, Blacklow SC. Notch signaling as a therapeutic target. Curr Opin Chem Biol. 2002;6(4):501–9.PubMedCrossRef Nam Y, Aster JC, Blacklow SC. Notch signaling as a therapeutic target. Curr Opin Chem Biol. 2002;6(4):501–9.PubMedCrossRef
36.
go back to reference Beatus P, Lundkvist J, Oberg C, Lendahl U. The notch 3 intracellular domain represses notch 1-mediated activation through Hairy/Enhancer of split (HES) promoters. Development. 1999;126(17):3925–35.PubMed Beatus P, Lundkvist J, Oberg C, Lendahl U. The notch 3 intracellular domain represses notch 1-mediated activation through Hairy/Enhancer of split (HES) promoters. Development. 1999;126(17):3925–35.PubMed
37.
go back to reference Forghanifard MM, Moaven O, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, et al. Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis. Ann Surg Oncol. 2012;19(3):743–9.PubMedCrossRef Forghanifard MM, Moaven O, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, et al. Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis. Ann Surg Oncol. 2012;19(3):743–9.PubMedCrossRef
38.
go back to reference Sang L, Roberts JM, Coller HA. Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells. Trends Mol Med. 2010;16(1):17–26. Sang L, Roberts JM, Coller HA. Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells. Trends Mol Med. 2010;16(1):17–26.
39.
go back to reference Katoh Y, Katoh M. Integrative genomic analyses on GLI1: positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES/HEY, and GPCR-Gs-PKA signals. Int J Oncol. 2009;35(1):187–92.PubMedCrossRef Katoh Y, Katoh M. Integrative genomic analyses on GLI1: positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES/HEY, and GPCR-Gs-PKA signals. Int J Oncol. 2009;35(1):187–92.PubMedCrossRef
40.
go back to reference Wall DS, Mears AJ, McNeill B, Mazerolle C, Thurig S, Wang Y, et al. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J Cell Biol. 2009;184(1):101–12.PubMedCentralPubMedCrossRef Wall DS, Mears AJ, McNeill B, Mazerolle C, Thurig S, Wang Y, et al. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J Cell Biol. 2009;184(1):101–12.PubMedCentralPubMedCrossRef
41.
go back to reference Kimura H, Kawasaki H, Taira K. Mouse microRNA-23b regulates expression of Hes1 gene in P19 cells. Nucleic Acids Symp Ser (Oxf). 2004;48:213–4.CrossRef Kimura H, Kawasaki H, Taira K. Mouse microRNA-23b regulates expression of Hes1 gene in P19 cells. Nucleic Acids Symp Ser (Oxf). 2004;48:213–4.CrossRef
42.
go back to reference Wang C, Yao N, Lu CL, Li D, Ma X. Mouse microRNA-124 regulates the expression of Hes1 in P19 cells. Front Biosci (Elite Ed). 2010;2:127–32.CrossRef Wang C, Yao N, Lu CL, Li D, Ma X. Mouse microRNA-124 regulates the expression of Hes1 in P19 cells. Front Biosci (Elite Ed). 2010;2:127–32.CrossRef
Metadata
Title
HES1 as an Independent Prognostic Marker in Esophageal Squamous Cell Carcinoma
Authors
Shaghayegh Taleb
Mohammad Reza Abbaszadegan
Meysam Moghbeli
Nasim Hayati Roudbari
Mohammad Mahdi Forghanifard
Publication date
01-12-2014
Publisher
Springer US
Published in
Journal of Gastrointestinal Cancer / Issue 4/2014
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-014-9648-1

Other articles of this Issue 4/2014

Journal of Gastrointestinal Cancer 4/2014 Go to the issue