Initiator of Colon Cancer Metastasis Identified

A recent study highlighted the role of the BVES (blood vessel epicardial substance) protein in the epithelial-mesenchymal transition (EMT) that occurs when the cells comprising a primary tumor begin to spread and metastasize.

The acquisition of a mesenchymal phenotype is a critical step in the metastatic progression of epithelial cancers. Adherens junctions (AJs) are required for suppressing EMT but less is known about the role of tight junctions (TJs) in this process. To elucidate further the factors that drive EMT, investigators at Vanderbilt University (Nashville, TN, USA) examined the function of BVES (also known as POPDC1 and POP1) in relation to the initiation of EMT.

BVES is a highly conserved, transmembrane protein that is involved in cell adhesion, cell motility, and most recently has been shown to play a role in vesicular transport. BVES is found in a wide variety of organisms (from flies to humans) and is a member of the evolutionarily conserved Popdc family of proteins. Although the precise molecular function of BVES is unknown, disruption of this protein results in a wide range of developmental defects and impaired cellular processes.

The investigators reported in the September 12, 2011, online edition of the Journal of Clinical Investigation that they had found that BVES was underexpressed in all stages of human colorectal carcinoma (CRC) and in adenomatous polyps, indicating that its suppression occurred early in transformation. At the genomic level, they found that the BVES promoter was heavily methylated, which silenced its expression. Treating cells that were undergoing EMT with a demethylating agent (the drug decitabine, which is currently used to treat myelodysplastic disorders) restored BVES expression. Renewed BVES expression caused the cells to become more epithelial in nature, and their prometastatic characteristics diminished.

“In cancer, typically the primary tumor does not kill you; it is the metastatic disease that proves lethal," said first author Dr. Christopher Williams, assistant professor of medicine and cancer biology at Vanderbilt University. “So, if targeting BVES could interfere with metastasis; that would be very exciting.”

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