Disruption of proteins expressed at the junctures between cells (known as tight junctions) is a hallmark of cancer cell invasion and spread (metastasis).
Recent studies have shown that changes in the family of tight junction proteins known as claudins occur during tumor initiation and growth, however no causal link between claudin expression and cancer has been demonstrated.
In a study appearing online on June 16 in advance of print publication in the July 1 issue of the Journal of Clinical Investigation, Punita Dhawan and colleagues from Vanderbilt University report increased expression of claudin-1 in human primary colon carcinomas and metastases.
They also found that instead of being normally expressed in the cell membrane, claudin-1 was instead located in the colon cancer cell nucleus and cytoplasm. Those cancer cells that metastasized from the primary tumor site were found to express the highest levels of claudin-1 and also exhibited a greater degree of claudin-1 mislocalization.
Using genetically manipulated colorectal cancer cells, the authors demonstrate a role for claudin-1 in the regulation of cellular transformation, tumor growth, and spread and identify, in part, the cellular pathways involved in claudin-1 overexpression.
These observations raise the possibility that claudin-1 may be exploited as a potential biomarker for colon cancer progression and may also provide new opportunities for therapeutic intervention.