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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Kidney Cancer | Research

A comprehensive analysis of different types of databases reveals that CDH1 mRNA and E-cadherin protein are not downregulated in most carcinoma tissues and carcinoma cell lines

Authors: Brihget Sicairos, Shorna Alam, Yuchun Du

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

The CDH1 gene codes for the epithelial-cadherin (E-cad) protein, which is embedded in the plasma membrane of epithelial cells to form adherens junctions. E-cad is known to be essential for maintaining the integrity of epithelial tissues, and the loss of E-cad has been widely considered a hallmark of metastatic cancers enabling carcinoma cells to acquire the ability to migrate and invade nearby tissues. However, this conclusion has come under scrutiny.

Methods

To assess how CDH1 and E-cad expression changes during cancer progression, we analyzed multiple large transcriptomics, proteomics, and immunohistochemistry datasets on clinical cancer samples and cancer cell lines to determine the CDH1 mRNA and E-cad protein expression profiles in tumor and normal cells.

Results

In contrast to the textbook knowledge of the loss of E-cad during tumor progression and metastasis, the levels of CDH1 mRNA and E-cad protein are either upregulated or remain unchanged in most carcinoma cells compared to normal cells. In addition, the CDH1 mRNA upregulation occurs in the early stages of tumor development and the levels remain elevated as tumors progress to later stages across most carcinoma types. Furthermore, E-cad protein levels are not downregulated in most metastatic tumor cells compared to primary tumor cells. The CDH1 mRNA and E-cad protein levels are positively correlated, and the CDH1 mRNA levels are positively correlated to cancer patient’s survival. We have discussed potential mechanisms underlying the observed expression changes in CDH1 and E-cad during tumor progression.

Conclusions

CDH1 mRNA and E-cadherin protein are not downregulated in most tumor tissues and cell lines derived from commonly occurring carcinomas. The role of E-cad in tumor progression and metastasis may have previously been oversimplified. CDH1 mRNA levels may serve as a reliable biomarker for the diagnosis of some tumors (such as colon and endometrial carcinomas) due to the marked upregulation of CDH1 mRNA in the early stages of tumor development of these carcinomas.
Appendix
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Literature
2.
3.
go back to reference Coopman P, Djiane A. Adherens Junction and E-Cadherin complex regulation by epithelial polarity. Cell Mol Life Sci. 2016;73(18):3535–53.PubMedCrossRef Coopman P, Djiane A. Adherens Junction and E-Cadherin complex regulation by epithelial polarity. Cell Mol Life Sci. 2016;73(18):3535–53.PubMedCrossRef
4.
go back to reference Boggon TJ, Murray J, Chappuis-Flament S, Wong E, Gumbiner BM, Shapiro L. C-cadherin ectodomain structure and implications for cell adhesion mechanisms. Science. 2002;296(5571):1308–13.PubMedCrossRef Boggon TJ, Murray J, Chappuis-Flament S, Wong E, Gumbiner BM, Shapiro L. C-cadherin ectodomain structure and implications for cell adhesion mechanisms. Science. 2002;296(5571):1308–13.PubMedCrossRef
5.
go back to reference Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988;102(4):639–55.PubMedCrossRef Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988;102(4):639–55.PubMedCrossRef
6.
go back to reference Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20(23):3199–214.PubMedCrossRef Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20(23):3199–214.PubMedCrossRef
7.
go back to reference Overduin M, Harvey TS, Bagby S, Tong KI, Yau P, Takeichi M, Ikura M. Solution structure of the epithelial cadherin domain responsible for selective cell adhesion. Science. 1995;267(5196):386–9.PubMedCrossRef Overduin M, Harvey TS, Bagby S, Tong KI, Yau P, Takeichi M, Ikura M. Solution structure of the epithelial cadherin domain responsible for selective cell adhesion. Science. 1995;267(5196):386–9.PubMedCrossRef
8.
go back to reference Parisini E, Higgins JM, Liu JH, Brenner MB, Wang JH. The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism. J Mol Biol. 2007;373(2):401–11.PubMedPubMedCentralCrossRef Parisini E, Higgins JM, Liu JH, Brenner MB, Wang JH. The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism. J Mol Biol. 2007;373(2):401–11.PubMedPubMedCentralCrossRef
10.
go back to reference Le Bras GF, Taubenslag KJ, Andl CD. The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression. Cell Adh Migr. 2012;6(4):365–73.PubMedPubMedCentralCrossRef Le Bras GF, Taubenslag KJ, Andl CD. The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression. Cell Adh Migr. 2012;6(4):365–73.PubMedPubMedCentralCrossRef
12.
14.
go back to reference Berx G, Cleton-Jansen AM, Nollet F, de Leeuw WJ, van de Vijver M, Cornelisse C, van Roy F. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J. 1995;14(24):6107–15.PubMedPubMedCentralCrossRef Berx G, Cleton-Jansen AM, Nollet F, de Leeuw WJ, van de Vijver M, Cornelisse C, van Roy F. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J. 1995;14(24):6107–15.PubMedPubMedCentralCrossRef
15.
go back to reference Liu J, Sun X, Qin S, Wang H, Du N, Li Y, Pang Y, Wang C, Xu C, Ren H. CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer. Oncol Lett. 2016;11(4):2635–43.PubMedPubMedCentralCrossRef Liu J, Sun X, Qin S, Wang H, Du N, Li Y, Pang Y, Wang C, Xu C, Ren H. CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer. Oncol Lett. 2016;11(4):2635–43.PubMedPubMedCentralCrossRef
19.
go back to reference Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68(10):3645–54.PubMedCrossRef Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68(10):3645–54.PubMedCrossRef
22.
go back to reference Lou Y, Preobrazhenska O. auf dem Keller U, Sutcliffe M, Barclay L, McDonald PC, Roskelley C, Overall CM, Dedhar S: Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Dev Dyn. 2008;237(10):2755–68.PubMedCrossRef Lou Y, Preobrazhenska O. auf dem Keller U, Sutcliffe M, Barclay L, McDonald PC, Roskelley C, Overall CM, Dedhar S: Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Dev Dyn. 2008;237(10):2755–68.PubMedCrossRef
23.
go back to reference Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015;527(7579):472–6.PubMedPubMedCentralCrossRef Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015;527(7579):472–6.PubMedPubMedCentralCrossRef
24.
go back to reference Shamir ER, Pappalardo E, Jorgens DM, Coutinho K, Tsai WT, Aziz K, Auer M, Tran PT, Bader JS, Ewald AJ. Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. J Cell Biol. 2014;204(5):839–56.PubMedPubMedCentralCrossRef Shamir ER, Pappalardo E, Jorgens DM, Coutinho K, Tsai WT, Aziz K, Auer M, Tran PT, Bader JS, Ewald AJ. Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. J Cell Biol. 2014;204(5):839–56.PubMedPubMedCentralCrossRef
25.
go back to reference Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS, Kalluri R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015;527(7579):525–30.PubMedPubMedCentralCrossRef Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS, Kalluri R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015;527(7579):525–30.PubMedPubMedCentralCrossRef
26.
go back to reference Bukholm IK, Nesland JM, Karesen R, Jacobsen U, Borresen-Dale AL. E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol. 1998;185(3):262–6.PubMedCrossRef Bukholm IK, Nesland JM, Karesen R, Jacobsen U, Borresen-Dale AL. E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol. 1998;185(3):262–6.PubMedCrossRef
27.
go back to reference Park SY, Jang H, Kim SY, Kim D, Park Y, Kee SH. Expression of E-Cadherin in Epithelial cancer cells Increases cell motility and directionality through the localization of ZO-1 during collective cell migration. Bioengineering (Basel). 2021;8(5):65.PubMedCrossRef Park SY, Jang H, Kim SY, Kim D, Park Y, Kee SH. Expression of E-Cadherin in Epithelial cancer cells Increases cell motility and directionality through the localization of ZO-1 during collective cell migration. Bioengineering (Basel). 2021;8(5):65.PubMedCrossRef
28.
go back to reference Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818–29.PubMedCrossRef Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818–29.PubMedCrossRef
30.
go back to reference Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–102.PubMedPubMedCentralCrossRef Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–102.PubMedPubMedCentralCrossRef
31.
go back to reference Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–60.PubMedPubMedCentralCrossRef Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–60.PubMedPubMedCentralCrossRef
32.
go back to reference Consortium GT. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45(6):580–5.CrossRef Consortium GT. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45(6):580–5.CrossRef
33.
go back to reference Ghandi M, Huang FW, Jane-Valbuena J, Kryukov GV, Lo CC, McDonald ER 3rd, Barretina J, Gelfand ET, Bielski CM, Li H, et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019;569(7757):503–8.PubMedPubMedCentralCrossRef Ghandi M, Huang FW, Jane-Valbuena J, Kryukov GV, Lo CC, McDonald ER 3rd, Barretina J, Gelfand ET, Bielski CM, Li H, et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019;569(7757):503–8.PubMedPubMedCentralCrossRef
34.
go back to reference Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483(7391):603–7.PubMedPubMedCentralCrossRef Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483(7391):603–7.PubMedPubMedCentralCrossRef
35.
go back to reference Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, Varambally S. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649–58.PubMedPubMedCentralCrossRef Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, Varambally S. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649–58.PubMedPubMedCentralCrossRef
36.
go back to reference Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, Netto GJ, Qin ZS, Kumar S, Manne U, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18–27.PubMedPubMedCentralCrossRef Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, Netto GJ, Qin ZS, Kumar S, Manne U, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18–27.PubMedPubMedCentralCrossRef
37.
go back to reference Chen F, Chandrashekar DS, Varambally S, Creighton CJ. Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers. Nat Commun. 2019;10(1):5679.PubMedPubMedCentralCrossRef Chen F, Chandrashekar DS, Varambally S, Creighton CJ. Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers. Nat Commun. 2019;10(1):5679.PubMedPubMedCentralCrossRef
38.
go back to reference Nusinow DP, Szpyt J, Ghandi M, Rose CM, McDonald ER 3rd, Kalocsay M, Jane-Valbuena J, Gelfand E, Schweppe DK, Jedrychowski M, et al. Quantitative proteomics of the cancer cell line encyclopedia. Cell. 2020;180(2):387-402 e316.PubMedPubMedCentralCrossRef Nusinow DP, Szpyt J, Ghandi M, Rose CM, McDonald ER 3rd, Kalocsay M, Jane-Valbuena J, Gelfand E, Schweppe DK, Jedrychowski M, et al. Quantitative proteomics of the cancer cell line encyclopedia. Cell. 2020;180(2):387-402 e316.PubMedPubMedCentralCrossRef
39.
go back to reference Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C, et al. A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics. 2005;4(12):1920–32.PubMedCrossRef Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C, et al. A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics. 2005;4(12):1920–32.PubMedCrossRef
40.
go back to reference Monsivais D, Vasquez YM, Chen F, Zhang Y, Chandrashekar DS, Faver JC, Masand RP, Scheurer ME, Varambally S, Matzuk MM, et al. Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers. Oncogene. 2021;40(11):2081–95.PubMedPubMedCentralCrossRef Monsivais D, Vasquez YM, Chen F, Zhang Y, Chandrashekar DS, Faver JC, Masand RP, Scheurer ME, Varambally S, Matzuk MM, et al. Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers. Oncogene. 2021;40(11):2081–95.PubMedPubMedCentralCrossRef
41.
go back to reference Wendt MK, Taylor MA, Schiemann BJ, Schiemann WP. Down-regulation of epithelial cadherin is required to initiate metastatic outgrowth of breast cancer. Mol Biol Cell. 2011;22(14):2423–35.PubMedPubMedCentralCrossRef Wendt MK, Taylor MA, Schiemann BJ, Schiemann WP. Down-regulation of epithelial cadherin is required to initiate metastatic outgrowth of breast cancer. Mol Biol Cell. 2011;22(14):2423–35.PubMedPubMedCentralCrossRef
42.
go back to reference Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell. 2005;123(5):903–15.PubMedPubMedCentralCrossRef Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell. 2005;123(5):903–15.PubMedPubMedCentralCrossRef
43.
go back to reference Campbell K, Casanova J. A role for E-cadherin in ensuring cohesive migration of a heterogeneous population of non-epithelial cells. Nat Commun. 2015;6:7998.PubMedCrossRef Campbell K, Casanova J. A role for E-cadherin in ensuring cohesive migration of a heterogeneous population of non-epithelial cells. Nat Commun. 2015;6:7998.PubMedCrossRef
44.
go back to reference Koussounadis A, Langdon SP, Um IH, Harrison DJ, Smith VA. Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system. Sci Rep. 2015;5:10775.PubMedPubMedCentralCrossRef Koussounadis A, Langdon SP, Um IH, Harrison DJ, Smith VA. Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system. Sci Rep. 2015;5:10775.PubMedPubMedCentralCrossRef
45.
46.
go back to reference Ramazi S, Zahiri J: Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford) 2021, 2021:baab012PubMedCrossRef Ramazi S, Zahiri J: Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford) 2021, 2021:baab012PubMedCrossRef
47.
go back to reference Vaklavas C, Blume SW, Grizzle WE. Translational dysregulation in cancer: molecular insights and potential clinical applications in biomarker development. Front Oncol. 2017;7:158.PubMedPubMedCentralCrossRef Vaklavas C, Blume SW, Grizzle WE. Translational dysregulation in cancer: molecular insights and potential clinical applications in biomarker development. Front Oncol. 2017;7:158.PubMedPubMedCentralCrossRef
49.
go back to reference Yang H, Hu HY. Sequestration of cellular interacting partners by protein aggregates: implication in a loss-of-function pathology. FEBS J. 2016;283(20):3705–17.PubMedCrossRef Yang H, Hu HY. Sequestration of cellular interacting partners by protein aggregates: implication in a loss-of-function pathology. FEBS J. 2016;283(20):3705–17.PubMedCrossRef
50.
go back to reference Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M, Cano A. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol. 1993;142(4):987–93.PubMedPubMedCentral Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M, Cano A. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol. 1993;142(4):987–93.PubMedPubMedCentral
51.
go back to reference Moll R, Mitze M, Frixen UH, Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol. 1993;143(6):1731–42.PubMedPubMedCentral Moll R, Mitze M, Frixen UH, Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol. 1993;143(6):1731–42.PubMedPubMedCentral
52.
go back to reference Rasbridge SA, Gillett CE, Sampson SA, Walsh FS, Millis RR. Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol. 1993;169(2):245–50.PubMedCrossRef Rasbridge SA, Gillett CE, Sampson SA, Walsh FS, Millis RR. Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol. 1993;169(2):245–50.PubMedCrossRef
53.
go back to reference Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83.PubMedCrossRef Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83.PubMedCrossRef
54.
go back to reference Huang RY, Guilford P, Thiery JP. Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci. 2012;125(Pt 19):4417–22.PubMedCrossRef Huang RY, Guilford P, Thiery JP. Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci. 2012;125(Pt 19):4417–22.PubMedCrossRef
55.
go back to reference Graff JR, Greenberg VE, Herman JG, Westra WH, Boghaert ER, Ain KB, Saji M, Zeiger MA, Zimmer SG, Baylin SB. Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle’s cell, and poorly differentiated human thyroid carcinoma. Cancer Res. 1998;58(10):2063–6.PubMed Graff JR, Greenberg VE, Herman JG, Westra WH, Boghaert ER, Ain KB, Saji M, Zeiger MA, Zimmer SG, Baylin SB. Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle’s cell, and poorly differentiated human thyroid carcinoma. Cancer Res. 1998;58(10):2063–6.PubMed
56.
go back to reference Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG. Methylation patterns of the E-cadherin 5’ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem. 2000;275(4):2727–32.PubMedCrossRef Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG. Methylation patterns of the E-cadherin 5’ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem. 2000;275(4):2727–32.PubMedCrossRef
57.
go back to reference Nass SJ, Herman JG, Gabrielson E, Iversen PW, Parl FF, Davidson NE, Graff JR. Aberrant methylation of the estrogen receptor and E-cadherin 5’ CpG islands increases with malignant progression in human breast cancer. Cancer Res. 2000;60(16):4346–8.PubMed Nass SJ, Herman JG, Gabrielson E, Iversen PW, Parl FF, Davidson NE, Graff JR. Aberrant methylation of the estrogen receptor and E-cadherin 5’ CpG islands increases with malignant progression in human breast cancer. Cancer Res. 2000;60(16):4346–8.PubMed
58.
go back to reference Lombaerts M, van Wezel T, Philippo K, Dierssen JW, Zimmerman RM, Oosting J, van Eijk R, Eilers PH, van de Water B, Cornelisse CJ. et al. E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br J Cancer. 2006, 94(5):661–671.PubMedPubMedCentralCrossRef Lombaerts M, van Wezel T, Philippo K, Dierssen JW, Zimmerman RM, Oosting J, van Eijk R, Eilers PH, van de Water B, Cornelisse CJ. et al. E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br J Cancer. 2006, 94(5):661–671.PubMedPubMedCentralCrossRef
59.
go back to reference Raeber GP, Lutolf MP, Hubbell JA. Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. Biophys J. 2005;89(2):1374–88.PubMedPubMedCentralCrossRef Raeber GP, Lutolf MP, Hubbell JA. Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. Biophys J. 2005;89(2):1374–88.PubMedPubMedCentralCrossRef
60.
go back to reference EslamiAmirabadi H, Tuerlings M, Hollestelle A, SahebAli S, Luttge R, van Donkelaar CC, Martens JWM, den Toonder JMJ. Characterizing the invasion of different breast cancer cell lines with distinct E-cadherin status in 3D using a microfluidic system. Biomed Microdevices. 2019;21(4):101.CrossRef EslamiAmirabadi H, Tuerlings M, Hollestelle A, SahebAli S, Luttge R, van Donkelaar CC, Martens JWM, den Toonder JMJ. Characterizing the invasion of different breast cancer cell lines with distinct E-cadherin status in 3D using a microfluidic system. Biomed Microdevices. 2019;21(4):101.CrossRef
61.
go back to reference Cancer Genome Atlas Research N. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.CrossRef Cancer Genome Atlas Research N. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.CrossRef
62.
go back to reference Gu T, Zhao X. Integrating multi-platform genomic datasets for kidney renal clear cell carcinoma subtyping using stacked denoising autoencoders. Sci Rep. 2019;9(1):16668.PubMedPubMedCentralCrossRef Gu T, Zhao X. Integrating multi-platform genomic datasets for kidney renal clear cell carcinoma subtyping using stacked denoising autoencoders. Sci Rep. 2019;9(1):16668.PubMedPubMedCentralCrossRef
64.
go back to reference Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009;10(7):445–57.PubMedCrossRef Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009;10(7):445–57.PubMedCrossRef
67.
go back to reference Pastushenko I, Blanpain C. EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol. 2019;29(3):212–26.PubMedCrossRef Pastushenko I, Blanpain C. EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol. 2019;29(3):212–26.PubMedCrossRef
68.
go back to reference Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Campbell K, Cano A, Casanova J, Christofori G, et al. Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2020;21(6):341–52.PubMedPubMedCentralCrossRef Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Campbell K, Cano A, Casanova J, Christofori G, et al. Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2020;21(6):341–52.PubMedPubMedCentralCrossRef
69.
go back to reference Ayollo DV, Zhitnyak IY, Vasiliev JM, Gloushankova NA. Rearrangements of the actin cytoskeleton and E-cadherin-based adherens junctions caused by neoplasic transformation change cell-cell interactions. PLoS One. 2009;4(11):e8027.PubMedPubMedCentralCrossRef Ayollo DV, Zhitnyak IY, Vasiliev JM, Gloushankova NA. Rearrangements of the actin cytoskeleton and E-cadherin-based adherens junctions caused by neoplasic transformation change cell-cell interactions. PLoS One. 2009;4(11):e8027.PubMedPubMedCentralCrossRef
70.
go back to reference Padmanaban V, Krol I, Suhail Y, Szczerba BM, Aceto N, Bader JS, Ewald AJ. E-cadherin is required for metastasis in multiple models of breast cancer. Nature. 2019;573(7774):439–44.PubMedPubMedCentralCrossRef Padmanaban V, Krol I, Suhail Y, Szczerba BM, Aceto N, Bader JS, Ewald AJ. E-cadherin is required for metastasis in multiple models of breast cancer. Nature. 2019;573(7774):439–44.PubMedPubMedCentralCrossRef
71.
go back to reference Na TY, Schecterson L, Mendonsa AM, Gumbiner BM. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. Proc Natl Acad Sci U S A. 2020;117(11):5931–7.PubMedPubMedCentralCrossRef Na TY, Schecterson L, Mendonsa AM, Gumbiner BM. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. Proc Natl Acad Sci U S A. 2020;117(11):5931–7.PubMedPubMedCentralCrossRef
72.
go back to reference Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta. 2007;1773(5):642–52.PubMedCrossRef Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta. 2007;1773(5):642–52.PubMedCrossRef
73.
go back to reference Barkan D, El Touny LH, Michalowski AM, Smith JA, Chu I, Davis AS, Webster JD, Hoover S, Simpson RM, Gauldie J, et al. Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res. 2010;70(14):5706–16.PubMedPubMedCentralCrossRef Barkan D, El Touny LH, Michalowski AM, Smith JA, Chu I, Davis AS, Webster JD, Hoover S, Simpson RM, Gauldie J, et al. Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res. 2010;70(14):5706–16.PubMedPubMedCentralCrossRef
74.
go back to reference Vallorosi CJ, Day KC, Zhao X, Rashid MG, Rubin MA, Johnson KR, Wheelock MJ, Day ML. Truncation of the beta-catenin binding domain of E-cadherin precedes epithelial apoptosis during prostate and mammary involution. J Biol Chem. 2000;275(5):3328–34.PubMedCrossRef Vallorosi CJ, Day KC, Zhao X, Rashid MG, Rubin MA, Johnson KR, Wheelock MJ, Day ML. Truncation of the beta-catenin binding domain of E-cadherin precedes epithelial apoptosis during prostate and mammary involution. J Biol Chem. 2000;275(5):3328–34.PubMedCrossRef
75.
go back to reference Fouquet S, Lugo-Martinez VH, Faussat AM, Renaud F, Cardot P, Chambaz J, Pincon-Raymond M, Thenet S. Early loss of E-cadherin from cell-cell contacts is involved in the onset of Anoikis in enterocytes. J Biol Chem. 2004;279(41):43061–9.PubMedCrossRef Fouquet S, Lugo-Martinez VH, Faussat AM, Renaud F, Cardot P, Chambaz J, Pincon-Raymond M, Thenet S. Early loss of E-cadherin from cell-cell contacts is involved in the onset of Anoikis in enterocytes. J Biol Chem. 2004;279(41):43061–9.PubMedCrossRef
76.
go back to reference Masszi A, Di Ciano C, Sirokmany G, Arthur WT, Rotstein OD, Wang J, McCulloch CA, Rosivall L, Mucsi I, Kapus A. Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition. Am J Physiol Renal Physiol. 2003;284(5):F911-924.PubMedCrossRef Masszi A, Di Ciano C, Sirokmany G, Arthur WT, Rotstein OD, Wang J, McCulloch CA, Rosivall L, Mucsi I, Kapus A. Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition. Am J Physiol Renal Physiol. 2003;284(5):F911-924.PubMedCrossRef
77.
go back to reference Tian YC, Fraser D, Attisano L, Phillips AO. TGF-beta1-mediated alterations of renal proximal tubular epithelial cell phenotype. Am J Physiol Renal Physiol. 2003;285(1):F130-142.PubMedCrossRef Tian YC, Fraser D, Attisano L, Phillips AO. TGF-beta1-mediated alterations of renal proximal tubular epithelial cell phenotype. Am J Physiol Renal Physiol. 2003;285(1):F130-142.PubMedCrossRef
78.
79.
go back to reference Naber HP, Drabsch Y, Snaar-Jagalska BE, ten Dijke P, van Laar T. Snail and Slug, key regulators of TGF-beta-induced EMT, are sufficient for the induction of single-cell invasion. Biochem Biophys Res Commun. 2013;435(1):58–63.PubMedCrossRef Naber HP, Drabsch Y, Snaar-Jagalska BE, ten Dijke P, van Laar T. Snail and Slug, key regulators of TGF-beta-induced EMT, are sufficient for the induction of single-cell invasion. Biochem Biophys Res Commun. 2013;435(1):58–63.PubMedCrossRef
80.
go back to reference Lintz M, Munoz A, Reinhart-King CA: The Mechanics of Single Cell and Collective Migration of Tumor Cells. J Biomech Eng. 2017;139(2):021005–9. Lintz M, Munoz A, Reinhart-King CA: The Mechanics of Single Cell and Collective Migration of Tumor Cells. J Biomech Eng. 2017;139(2):021005–9.
81.
go back to reference Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158(5):1110–22.PubMedPubMedCentralCrossRef Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158(5):1110–22.PubMedPubMedCentralCrossRef
82.
go back to reference Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, Priest LJ, Greystoke A, Zhou C, Morris K, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol. 2012;30(5):525–32.PubMedCrossRef Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, Priest LJ, Greystoke A, Zhou C, Morris K, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol. 2012;30(5):525–32.PubMedCrossRef
83.
go back to reference Peela N, Sam FS, Christenson W, Truong D, Watson AW, Mouneimne G, Ros R, Nikkhah M. A three dimensional micropatterned tumor model for breast cancer cell migration studies. Biomaterials. 2016;81:72–83.PubMedCrossRef Peela N, Sam FS, Christenson W, Truong D, Watson AW, Mouneimne G, Ros R, Nikkhah M. A three dimensional micropatterned tumor model for breast cancer cell migration studies. Biomaterials. 2016;81:72–83.PubMedCrossRef
84.
go back to reference Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J. Garcia De Herreros A: The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000;2(2):84–9.PubMedCrossRef Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J. Garcia De Herreros A: The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000;2(2):84–9.PubMedCrossRef
85.
go back to reference Nabeshima K, Inoue T, Shimao Y, Kataoka H, Koono M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol Histopathol. 1999;14(4):1183–97.PubMed Nabeshima K, Inoue T, Shimao Y, Kataoka H, Koono M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol Histopathol. 1999;14(4):1183–97.PubMed
86.
go back to reference Wang X, Enomoto A, Asai N, Kato T, Takahashi M. Collective invasion of cancer: Perspectives from pathology and development. Pathol Int. 2016;66(4):183–92.PubMedCrossRef Wang X, Enomoto A, Asai N, Kato T, Takahashi M. Collective invasion of cancer: Perspectives from pathology and development. Pathol Int. 2016;66(4):183–92.PubMedCrossRef
87.
go back to reference Cheung KJ, Padmanaban V, Silvestri V, Schipper K, Cohen JD, Fairchild AN, Gorin MA, Verdone JE, Pienta KJ, Bader JS, et al. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc Natl Acad Sci U S A. 2016;113(7):E854-863.PubMedPubMedCentralCrossRef Cheung KJ, Padmanaban V, Silvestri V, Schipper K, Cohen JD, Fairchild AN, Gorin MA, Verdone JE, Pienta KJ, Bader JS, et al. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc Natl Acad Sci U S A. 2016;113(7):E854-863.PubMedPubMedCentralCrossRef
88.
go back to reference Friedl P, Locker J, Sahai E, Segall JE. Classifying collective cancer cell invasion. Nat Cell Biol. 2012;14(8):777–83.PubMedCrossRef Friedl P, Locker J, Sahai E, Segall JE. Classifying collective cancer cell invasion. Nat Cell Biol. 2012;14(8):777–83.PubMedCrossRef
89.
go back to reference Chao YL, Shepard CR, Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer. 2010;9:179.PubMedPubMedCentralCrossRef Chao YL, Shepard CR, Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer. 2010;9:179.PubMedPubMedCentralCrossRef
90.
go back to reference Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66(17):8319–26.PubMedCrossRef Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66(17):8319–26.PubMedCrossRef
Metadata
Title
A comprehensive analysis of different types of databases reveals that CDH1 mRNA and E-cadherin protein are not downregulated in most carcinoma tissues and carcinoma cell lines
Authors
Brihget Sicairos
Shorna Alam
Yuchun Du
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10916-0

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