Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer

Punita Dhawan, Amar Bahadur Singh, Natasha G. Deane, Yi Ran No, Sheng Ru Shiou, Carl Schmidt, John Neff, M. Kay Washington, R. Daniel Beauchamp

Research output: Contribution to journalArticle

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Abstract

Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer cell invasion and metastasis. The role of adherent junction proteins has been studied extensively in cancer, but the roles of tight junction (TJ) proteins are less well understood. Claudins are recently identified members of the tetraspanin family of proteins, which are integral to the structure and function of TJs. Recent studies show changes in expression/cellular localization of claudins during tumorigenesis; however, a causal relationship between claudin expression/localization and cancer has not been established. Here, we report an increased expression of claudin-1 in human primary colon carcinoma and metastasis and in cell lines derived from primary and metastatic tumors. We also report frequent nuclear localization of claudin-1 in these samples. Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition. Furthermore, we demonstrate that changes in claudin-1 expression have significant effects on growth of xenografted tumors and metastasis in athymic mice. We further provide data suggesting that the regulation of E-cadherin expression and β-catenin/Tcf signaling is a possible mechanism underlying claudin-1-dependent changes.

Original languageEnglish (US)
Pages (from-to)1765-1776
Number of pages12
JournalJournal of Clinical Investigation
Volume115
Issue number7
DOIs
StatePublished - Jul 1 2005

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Claudin-1
Colonic Neoplasms
Claudins
Neoplasms
Neoplasm Metastasis
Tight Junction Proteins
Cell Line
Catenins
Proteins
Epithelial-Mesenchymal Transition
Intercellular Junctions
Cadherins
Nude Mice
Colon
Carcinogenesis
Carcinoma
Phenotype
Growth

ASJC Scopus subject areas

  • Medicine(all)

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Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. / Dhawan, Punita; Singh, Amar Bahadur; Deane, Natasha G.; No, Yi Ran; Shiou, Sheng Ru; Schmidt, Carl; Neff, John; Washington, M. Kay; Beauchamp, R. Daniel.

In: Journal of Clinical Investigation, Vol. 115, No. 7, 01.07.2005, p. 1765-1776.

Research output: Contribution to journalArticle

Dhawan, P, Singh, AB, Deane, NG, No, YR, Shiou, SR, Schmidt, C, Neff, J, Washington, MK & Beauchamp, RD 2005, 'Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer', Journal of Clinical Investigation, vol. 115, no. 7, pp. 1765-1776. https://doi.org/10.1172/JCI24543
Dhawan, Punita ; Singh, Amar Bahadur ; Deane, Natasha G. ; No, Yi Ran ; Shiou, Sheng Ru ; Schmidt, Carl ; Neff, John ; Washington, M. Kay ; Beauchamp, R. Daniel. / Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 7. pp. 1765-1776.
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