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

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 beta-catenin/Tcf signaling is a possible mechanism underlying claudin-1-dependent changes.

• Authors: Punita Dhawan, Amar B Singh, Natasha G Deane, Yiran No, Sheng-Ru Shiou, Carl Schmidt, John Neff, M Kay Washington, R Daniel Beauchamp
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 115 Issue 7 Pg. 1765-76 (Jul 2005) ISSN: 0021-9738 [Print] United States
• PMID: 15965503 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CLDN1 protein, human
• CTNNB1 protein, human
• CTNNB1 protein, mouse
• Claudin-1
• Cldn1 protein, mouse
• Cytoskeletal Proteins
• Membrane Proteins
• RNA, Small Interfering
• Trans-Activators
• beta Catenin

Topics

• Animals
• Cell Line, Tumor
• Cell Transformation, Neoplastic
• Claudin-1
• Colonic Neoplasms (etiology, genetics, pathology, secondary)
• Cytoskeletal Proteins (metabolism)
• Female
• Humans
• Membrane Proteins (antagonists & inhibitors, genetics, physiology)
• Mice
• Mice, Nude
• Neoplasm Metastasis (physiopathology)
• Neoplasm Transplantation
• RNA, Small Interfering (genetics)
• Signal Transduction
• Trans-Activators (metabolism)
• Transplantation, Heterologous
• beta Catenin