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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer

Authors: Ting Li, Hanqing Guo, Ying Song, Xiaodi Zhao, Yongquan Shi, Yuanyuan Lu, Sijun Hu, Yongzhan Nie, Daiming Fan, Kaichun Wu

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

Loss of cell-cell adhesion is important for the development of cancer invasion and metastasis. Vinculin, a key adhesion-related protein, can affect metastasis and prognosis in several tumours. Here, we determined the biological roles of vinculin in the metastasis of colorectal cancer (CRC) and evaluated its clinical significance as a potential disease biomarker.

Methods

The expression level of vinculin in CRC cell lines and tissues was measured using Real-Time PCR and western blotting. Moreover, vinculin function was analysed using Transwell assays and in vivo metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of vinculin together with membrane-bound β-catenin on the prognosis of 228 CRC patients was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in CRC tissues obtained from these patients.

Result

Vinculin expression was found to be significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Both in vitro and in vivo experiments showed that vinculin suppressed invasion, migration and metastasis in CRC cells and that this suppression could be attenuated by silencing β-catenin. Moreover, the expression of vinculin and membrane-bound β-catenin were positively correlated in CRC tissues, and lack of vinculin expression emerged as an independent prognostic factor in patients with CRC. Finally, the loss of vinculin and membrane-bound β-catenin was associated with node metastasis, organ metastasis and expression of EMT indicators.

Conclusion

Our results suggest that vinculin may play specific roles in the EMT and metastasis of CRC and that loss of vinculin could be used as a prognostic factor for CRC.
Appendix
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Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107CrossRefPubMed
2.
Center MM, Jemal A, Smith RA, Ward E: Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009, 59: 366-378. 10.3322/caac.20038CrossRefPubMed
3.
Mitry E, Bouvier AM, Esteve J, Faivre J: Benefit of operative mortality reduction on colorectal cancer survival. Br J Surg. 2002, 89: 1557-1562. 10.1046/j.1365-2168.2002.02276.xCrossRefPubMed
4.
Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-674. 10.1016/j.cell.2011.02.013CrossRefPubMed
5.
Cavallaro U, Christofori G: Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004, 4: 118-132. 10.1038/nrc1276CrossRefPubMed
6.
Ziegler WH, Liddington RC, Critchley DR: The structure and regulation of vinculin. Trends Cell Biol. 2006, 16: 453-460. 10.1016/j.tcb.2006.07.004CrossRefPubMed
7.
Humphries JD, Wang P, Streuli C, Geiger B, Humphries MJ, Ballestrem C: Vinculin controls focal adhesion formation by direct interactions with talin and actin. J Cell Biol. 2007, 179: 1043-1057. 10.1083/jcb.200703036PubMedCentralCrossRefPubMed
8.
Subauste MC, Pertz O, Adamson ED, Turner CE, Junger S, Hahn KM: Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility. J Cell Biol. 2004, 165: 371-381. 10.1083/jcb.200308011PubMedCentralCrossRefPubMed
9.
Wen KK, Rubenstein PA, DeMali KA: Vinculin nucleates actin polymerization and modifies actin filament structure. J Biol Chem. 2009, 284: 30463-30473. 10.1074/jbc.M109.021295PubMedCentralCrossRefPubMed
10.
Carisey A, Tsang R, Greiner AM, Nijenhuis N, Heath N, Nazgiewicz A, Kemkemer R, Derby B, Spatz J, Ballestrem C: Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner. Curr Biol. 2013, 23: 271-281. 10.1016/j.cub.2013.01.009PubMedCentralCrossRefPubMed
11.
Kawahara E, Tokuda R, Nakanishi I: Migratory phenotypes of HSC-3 squamous carcinoma cell line induced by EGF and PMA: relevance to migration of loosening of adhesion and vinculin-associated focal contacts with prominent filopodia. Cell Biol Int. 1999, 23: 163-174. 10.1006/cbir.1998.0331CrossRefPubMed
12.
Lifschitz-Mercer B, Czernobilsky B, Feldberg E, Geiger B: Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential. Hum Pathol. 1997, 28: 1230-1236. 10.1016/S0046-8177(97)90195-7CrossRefPubMed
13.
Meyer T, Brinck U: Immunohistochemical detection of vinculin in human rhabdomyosarcomas. Gen Diagn Pathol. 1997, 142: 191-198.PubMed
14.
Somiari RI, Sullivan A, Russell S, Somiari S, Hu H, Jordan R, George A, Katenhusen R, Buchowiecka A, Arciero C, Brzeski H, Hooke J, Shriver C: High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast. Proteomics. 2003, 3: 1863-1873. 10.1002/pmic.200300560CrossRefPubMed
15.
Yang HJ, Chen JZ, Zhang WL, Ding YQ: Focal adhesion plaque associated cytoskeletons are involved in the invasion and metastasis of human colorectal carcinoma. Cancer Invest. 2010, 28: 127-134. 10.3109/07357900903147184CrossRefPubMed
16.
Coll JL, Ben-Ze’Ev A, Ezzell RM, Rodriguez FJ, Baribault H, Oshima RG, Adamson ED: Targeted disruption of vinculin genes in F9 and embryonic stem cells changes cell morphology, adhesion, and locomotion. Proc Natl Acad Sci U S A. 1995, 92: 9161-9165. 10.1073/pnas.92.20.9161PubMedCentralCrossRefPubMed
17.
Rodriguez FJ, Geiger B, Salomon D, Sabanay I, Zoller M, Ben-Ze’Ev A: Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA. J Cell Biol. 1992, 119: 427-438. 10.1083/jcb.119.2.427CrossRef
18.
Gu S, Papadopoulou N: Activation of membrane androgen receptors in colon cancer inhibits the prosurvival signals Akt/Bad InVitroand InVivoand blocks migration via Vinculin/Actin signaling. Mol Med. 2011, 17: 1-CrossRef
19.
Bakolitsa C, Cohen DM, Bankston LA, Bobkov AA, Cadwell GW, Jennings L, Critchley DR, Craig SW, Liddington RC: Structural basis for vinculin activation at sites of cell adhesion. Nature. 2004, 430: 583-586. 10.1038/nature02610CrossRefPubMed
20.
Bois PR, O’Hara BP, Nietlispach D, Kirkpatrick J, Izard T: The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin. J Biol Chem. 2006, 281: 7228-7236. 10.1074/jbc.M510397200CrossRefPubMed
21.
Imamura Y, Itoh M, Maeno Y, Tsukita S, Nagafuchi A: Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion. J Cell Biol. 1999, 144: 1311-1322. 10.1083/jcb.144.6.1311PubMedCentralCrossRefPubMed
22.
Hazan RB, Kang L, Roe S, Borgen PI, Rimm DL: Vinculin is associated with the E-cadherin adhesion complex. J Biol Chem. 1997, 272: 32448-32453. 10.1074/jbc.272.51.32448CrossRefPubMed
23.
Peng X, Cuff LE, Lawton CD, DeMali KA: Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin. J Cell Sci. 2010, 123: 567-577. 10.1242/jcs.056432PubMedCentralCrossRefPubMed
24.
Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ: Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling. Hum Mol Genet. 2008, 17: 3105-3117. 10.1093/hmg/ddn208PubMedCentralCrossRefPubMed
25.
Stemmer V, de Craene B, Berx G, Behrens J: Snail promotes Wnt target gene expression and interacts with beta-catenin. Oncogene. 2008, 27: 5075-5080. 10.1038/onc.2008.140CrossRefPubMed
26.
Clevers H, Nusse R: Wnt/beta-catenin signaling and disease. Cell. 2012, 149: 1192-1205. 10.1016/j.cell.2012.05.012CrossRefPubMed
27.
Sanchez-Tillo E, de Barrios O, Siles L, Cuatrecasas M, Castells A, Postigo A: beta-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator ZEB1 to regulate tumor invasiveness. Proc Natl Acad Sci U S A. 2011, 108: 19204-19209. 10.1073/pnas.1108977108PubMedCentralCrossRefPubMed
28.
Dorudi S, Sheffield JP, Poulsom R, Northover JM, Hart IR: E-cadherin expression in colorectal cancer: an immunocytochemical and in situ hybridization study. Am J Pathol. 1993, 142: 981-986.PubMedCentralPubMed
29.
Ngan CY, Yamamoto H, Seshimo I, Tsujino T, Man-i M, Ikeda JI, Konishi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M: Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer. Br J Cancer. 2007, 96: 986-992. 10.1038/sj.bjc.6603651PubMedCentralCrossRefPubMed
30.
Ramesh S, Nash J, McCulloch PG: Reduction in membranous expression of beta-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer. Br J Cancer. 1999, 81: 1392-1397. 10.1038/sj.bjc.6693437PubMedCentralCrossRefPubMed
31.
Stanczak A, Stec R, Bodnar L, Olszewski W, Cichowicz M, Kozlowski W, Szczylik C, Pietrucha T, Wieczorek M, Lamparska-Przybysz M: Prognostic significance of Wnt-1, beta-catenin and E-cadherin expression in advanced colorectal carcinoma. Pathol Oncol Res. 2011, 17: 955-963. 10.1007/s12253-011-9409-4PubMedCentralCrossRefPubMed
32.
Hewitt RE, McMarlin A, Kleiner D, Wersto R, Martin P, Tsokos M, Stamp GW, Stetler-Stevenson WG: Validation of a model of colon cancer progression. J Pathol. 2000, 192: 446-454. 10.1002/1096-9896(2000)9999:9999<::AID-PATH775>3.0.CO;2-KCrossRefPubMed
33.
34.
Xu W, Baribault H, Adamson ED: Vinculin knockout results in heart and brain defects during embryonic development. Development. 1998, 125: 327-337.PubMed
35.
Mierke CT, Kollmannsberger P, Paranhos Zitterbart D, Smith J, Fabry B, Goldmann WH: Mechano-coupling and regulation of contractility by the vinculin tail domain. Biophys J. 2008, 94: 661-670. 10.1529/biophysj.107.108472PubMedCentralCrossRefPubMed
36.
Mierke CT, Kollmannsberger P, Zitterbart DP, Diez G, Koch TM, Marg S, Ziegler WH, Goldmann WH, Fabry B: Vinculin facilitates cell invasion into three-dimensional collagen matrices. J Biol Chem. 2010, 285: 13121-13130. 10.1074/jbc.M109.087171PubMedCentralCrossRefPubMed
37.
Chen H, Choudhury DM, Craig SW: Coincidence of actin filaments and talin is required to activate vinculin. J Biol Chem. 2006, 281: 40389-40398. 10.1074/jbc.M607324200CrossRefPubMed
38.
Subauste MC, Nalbant P, Adamson ED, Hahn KM: Vinculin controls PTEN protein level by maintaining the interaction of the adherens junction protein beta-catenin with the scaffolding protein MAGI-2. J Biol Chem. 2005, 280: 5676-5681. 10.1074/jbc.M405561200CrossRefPubMed
39.
40.
Solanas G, Porta-de-la-Riva M, Agusti C, Casagolda D, Sanchez-Aguilera F, Larriba MJ, Pons F, Peiro S, Escriva M, Munoz A, Dunach M, De Herreros AG, Baulida J: E-cadherin controls beta-catenin and NF-kappaB transcriptional activity in mesenchymal gene expression. J Cell Sci. 2008, 121: 2224-2234. 10.1242/jcs.021667CrossRefPubMed
41.
Kinugasa T, Akagi Y, Ochi T, Tanaka N, Kawahara A, Ishibashi Y, Gotanda Y, Yamaguchi K, Shiratuchi I, Oka Y, Kage M, Shirouzu K: Increased claudin-1 protein expression in hepatic metastatic lesions of colorectal cancer. Anticancer Res. 2012, 32: 2309-2314.PubMed
42.
Morikawa T, Kuchiba A, Yamauchi M, Meyerhardt JA, Shima K, Nosho K, Chan AT, Giovannucci E, Fuchs CS, Ogino S: Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. JAMA. 2011, 305: 1685-1694. 10.1001/jama.2011.513PubMedCentralCrossRefPubMed
43.
Choi HN, Kim KR, Lee JH, Park HS, Jang KY, Chung MJ, Hwang SE, Yu HC, Moon WS: Serum response factor enhances liver metastasis of colorectal carcinoma via alteration of the E-cadherin/beta-catenin complex. Oncol Rep. 2009, 21: 57-63.PubMed
44.
Shook D, Keller R: Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev. 2003, 120: 1351-1383. 10.1016/j.mod.2003.06.005CrossRefPubMed
45.
Polyak K, Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009, 9: 265-273. 10.1038/nrc2620CrossRefPubMed
46.
Yilmaz M, Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009, 28: 15-33. 10.1007/s10555-008-9169-0CrossRefPubMed
47.
Li T, Lu YY, Zhao XD, Guo HQ, Liu CH, Li H, Zhou L, Han YN, Wu KC, Nie YZ, Shi YQ, Fan DM: MicroRNA-296-5p increases proliferation in gastric cancer through repression of Caudal-related homeobox 1. Oncogene. 2014, 33: 783-793. 10.1038/onc.2012.637CrossRefPubMed
48.
Zhao X, Dou W, He L, Liang S, Tie J, Liu C, Li T, Lu Y, Mo P, Shi Y, Wu K, Nie Y, Fan D: MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor. Oncogene. 2013, 32: 1363-1372. 10.1038/onc.2012.156CrossRefPubMed
49.
Salim T, Sjolander A, Sand-Dejmek J: Nuclear expression of glycogen synthase kinase-3beta and lack of membranous beta-catenin is correlated with poor survival in colon cancer. Int J Cancer. 2013, 133: 807-815. 10.1002/ijc.28074CrossRefPubMed
50.
Neumann J, Horst D, Kriegl L, Maatz S, Engel J, Jung A, Kirchner T: A simple immunohistochemical algorithm predicts the risk of distant metastases in right-sided colon cancer. Histopathology. 2012, 60: 416-426. 10.1111/j.1365-2559.2011.04126.xCrossRefPubMed
51.
Uchikado Y, Natsugoe S, Okumura H, Setoyama T, Matsumoto M, Ishigami S, Aikou T: Slug Expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 2005, 11: 1174-1180.PubMed
Metadata
Title
Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer
Authors
Ting Li
Hanqing Guo
Ying Song
Xiaodi Zhao
Yongquan Shi
Yuanyuan Lu
Sijun Hu
Yongzhan Nie
Daiming Fan
Kaichun Wu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-263

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