Protein That Suppresses Invadopodia Formation Prevents Spread of Breast Cancer Cells

Elevated activity of the adaptor protein Cdc42-interacting protein 4 (CIP4) has been found to suppress the formation of invadopodia, actin-rich membrane protrusions that promote extracellular matrix (ECM) degradation and invasiveness of tumor cells.

Investigators at Queen's University (Kingston, ON, Canada) demonstrated the role of CIP4 by using RNA interference technology to block its activity in cultures of breast tumor cells.

They reported in the May 15, 2011, issue of the Journal of Cell Science that these CIP4 "knockdown” cells degraded more ECM, had increased numbers of mature invadopodia, and were more invasive through matrigel. The inhibitory role of CIP4 was explained by the finding that CIP4 limited surface expression of transmembrane type I matrix metalloprotease (MT1-MMP), by promoting MT1-MMP internalization. By removing this enzyme complex from the cell surface CIP4 suppressed invadopodia formation and reduced the ability of the cancer cells to metastasize.

"Cancer researchers want to design new therapeutic strategies in which the metastasis or spreading stage of cancer can be blocked,” explained senior author Dr. Andrew Craig, professor of biochemistry and cancer research at Queen's University. "Patients stand a much better chance of survival if the primary tumor is the only tumor that needs to be treated.”

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