EpCAM-claudin-tetraspanin-modulated Ovarian Cancer Progression and Drug Resistance

Overview

Journal Cell Adh Migr

Specialty Cell Biology

Date 2020 Feb 25

PMID 32091301

Citations 6

Authors

Zehra Tavsan

Hulya Ayar Kayali

Affiliations

Soon will be listed here.

Abstract

Alterations of cell adhesion are involved in cancer progression, but the mechanisms underlying the progression and cell adhesion have remained poorly understood. Focusing on the complex between EpCAM, claudins and tetraspanins, we described a sequence of events by which of the molecules associate each other in ovarian cancer. The interactions between molecules were evaluated by immunoprecipitations and then immunoblotting. To identify the effects of complex formation on the ovarian cancer progression, the different types of ovarian cancer cell lines were compared. In this study, we report the identification of the EpCAM-claudin-4 or -7-CD82 complex in the ovarian cancer progression and metastasis in vitro. Additionally, we demonstrated palmitoylation and intra- or extra-cellular regions are critically required for the complex formation. These results represent the first direct evidence for the link between the dynamism of cell adhesion molecules and ovarian cancer progression.

Citing Articles

zDHHC-Mediated S-Palmitoylation in Skin Health and Its Targeting as a Treatment Perspective.

Abdulrahman F, Benford K, Lin G, Maroun A, Sammons C, Shirzad D Int J Mol Sci. 2025; 26(4).

PMID: 40004137 PMC: 11854935. DOI: 10.3390/ijms26041673.

Regulation of the Function and Expression of EpCAM.

Xiao D, Xiong M, Wang X, Lyu M, Sun H, Cui Y Biomedicines. 2024; 12(5).

PMID: 38791091 PMC: 11117676. DOI: 10.3390/biomedicines12051129.

High-expressed ACAT2 predicted the poor prognosis of platinum-resistant epithelial ovarian cancer.

Wang J, Yang Z, Bai H, Zhao L, Ji J, Bin Y Diagn Pathol. 2024; 19(1):7.

PMID: 38178203 PMC: 10768435. DOI: 10.1186/s13000-023-01435-4.

Protein palmitoylation in cancer: molecular functions and therapeutic potential.

Zhou B, Hao Q, Liang Y, Kong E Mol Oncol. 2022; 17(1):3-26.

PMID: 36018061 PMC: 9812842. DOI: 10.1002/1878-0261.13308.

Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics.

Wang T, Gao Y, Wang X, Tian J, Li Y, Yu B Chin J Cancer Res. 2022; 34(2):95-108.

PMID: 35685992 PMC: 9086574. DOI: 10.21147/j.issn.1000-9604.2022.02.04.

References

Baldwin L, Hoff J, Lefringhouse J, Zhang M, Jia C, Liu Z . CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling. Oncotarget. 2014; 5(23):12203-17. PMC: 4322965. DOI: 10.18632/oncotarget.2622. View

Shogomori H, Hammond A, Ostermeyer-Fay A, Barr D, Feigenson G, London E . Palmitoylation and intracellular domain interactions both contribute to raft targeting of linker for activation of T cells. J Biol Chem. 2005; 280(19):18931-42. DOI: 10.1074/jbc.M500247200. View

Wodarz A, Nathke I . Cell polarity in development and cancer. Nat Cell Biol. 2007; 9(9):1016-24. DOI: 10.1038/ncb433. View

Uchida S, Shimada Y, Watanabe G, Li Z, Hong T, Miyake M . Motility-related protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer. 1999; 79(7-8):1168-73. PMC: 2362236. DOI: 10.1038/sj.bjc.6690186. View

Agarwal R, DSouza T, Morin P . Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res. 2005; 65(16):7378-85. DOI: 10.1158/0008-5472.CAN-05-1036. View

Schindl M, Birner P, Breitenecker G, Oberhuber G . Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer. Gynecol Oncol. 2001; 83(2):244-8. DOI: 10.1006/gyno.2001.6366. View

Schmidt D, Klingbeil P, Schnolzer M, Zoller M . CD44 variant isoforms associate with tetraspanins and EpCAM. Exp Cell Res. 2004; 297(2):329-47. DOI: 10.1016/j.yexcr.2004.02.023. View

Tayama S, Motohara T, Narantuya D, Li C, Fujimoto K, Sakaguchi I . The impact of EpCAM expression on response to chemotherapy and clinical outcomes in patients with epithelial ovarian cancer. Oncotarget. 2017; 8(27):44312-44325. PMC: 5546482. DOI: 10.18632/oncotarget.17871. View

Lu K, Patterson A, Wang L, Marquez R, Atkinson E, Baggerly K . Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res. 2004; 10(10):3291-300. DOI: 10.1158/1078-0432.CCR-03-0409. View

10.

Houle C, Ding X, Foley J, Afshari C, Barrett J, Davis B . Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression. Gynecol Oncol. 2002; 86(1):69-78. DOI: 10.1006/gyno.2002.6729. View

11.

Santin A, Zhan F, Bellone S, Palmieri M, Cane S, Bignotti E . Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy. Int J Cancer. 2004; 112(1):14-25. DOI: 10.1002/ijc.20408. View

12.

Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H . High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat. 2004; 86(3):207-13. DOI: 10.1023/B:BREA.0000036787.59816.01. View

13.

Nelson W . Adaptation of core mechanisms to generate cell polarity. Nature. 2003; 422(6933):766-74. PMC: 3373010. DOI: 10.1038/nature01602. View

14.

Spizzo G, Went P, Dirnhofer S, Obrist P, Moch H, Baeuerle P . Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol Oncol. 2006; 103(2):483-8. DOI: 10.1016/j.ygyno.2006.03.035. View

15.

Davidson B, Berner A, Nesland J, Risberg B, Berner H, Trope C . E-cadherin and alpha-, beta-, and gamma-catenin protein expression is up-regulated in ovarian carcinoma cells in serous effusions. J Pathol. 2000; 192(4):460-9. DOI: 10.1002/1096-9896(2000)9999:9999<::AID-PATH726>3.0.CO;2-M. View

16.

Park C, Kim T, Kim H, Kim Y, Jeoung M, Lee W . Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis. Oncogene. 2016; 35(34):4540-8. DOI: 10.1038/onc.2015.520. View

17.

Kovalenko O, Yang X, Hemler M . A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9. Mol Cell Proteomics. 2007; 6(11):1855-67. DOI: 10.1074/mcp.M700183-MCP200. View

18.

Philip R, Heiler S, Mu W, Buchler M, Zoller M, Thuma F . Claudin-7 promotes the epithelial-mesenchymal transition in human colorectal cancer. Oncotarget. 2014; 6(4):2046-63. PMC: 4385835. DOI: 10.18632/oncotarget.2858. View

19.

Liu F, Chen J, Dong J, Hsieh Y, Lin A, Ho E . KAI1 metastasis suppressor gene is frequently down-regulated in cervical carcinoma. Am J Pathol. 2001; 159(5):1629-34. PMC: 1867068. DOI: 10.1016/s0002-9440(10)63009-x. View

20.

Clancy J, Sedgwick A, Rosse C, Muralidharan-Chari V, Raposo G, Method M . Regulated delivery of molecular cargo to invasive tumour-derived microvesicles. Nat Commun. 2015; 6:6919. PMC: 4497525. DOI: 10.1038/ncomms7919. View