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Abstract

Claudins are tight junction proteins which along with adherens junctions and desmosomes form cellular sheets. Tight junctions (TJs) are critical for sealing the cellular sheets thereby controlling paracellular ion flux. The high degree of cellular organization typically observed in normally differentiated tissues is often lost in cancer. Loss of epithelial integrity with changing claudins levels and resultant increased para-cellular leakage plays a critical role in providing a space for tumor cell mobility and increased nutrientsâ?? supply for tumor cells underneath. Several studies analyzing the roles of tight junctions in oncogenesis have revealed either downregulation or upregulations of claudins expression. Claudins, whether upregulated or down regulated are proving to be a vital piece of the puzzle of oncogenesis. A prime example of the aforementioned role of claudins in carcinogenesis and metastases is claudin-1. It is one of the genes strongly regulated by B-catenin. The latter gene is known for its role in maintaining cell-to-cell adhesion and most importantly in mediating the oncogenic Wnt/B-catenin transduction pathway. Claudin-1 along with claudin-3 and claudin-5 are shown to promote pro-MMP2 whereby claudins recruit MMPs on the cell surface to achieve elevated focal concentrations and eventual activations of pro-MMP2. Claudin-1 expression is frequently altered in several cancers including upregulation and downregulation. In Colorectal cancer, claudin-1 plays an important role in oncogenesis and has been proven to have a prognostic value. In this talk, we present the role of claudin-1 as a biomarker of oncogenesis invasion and metastases in colorectal cancer. We also address some of the controversies surrounding the use of claudin-1 as a biomarker of G.I. tumors. Lastly, we summarize our recommendations for the type of cases where claudins should be utilized as biomarkers of oncogenesis and invasion.

Biography