Study Shows How Cancerous Epithelial Cells Evade Cellular Defenses

Researchers in Japan have discovered a mechanism by which cancerous epithelial cells evade cellular defenses and become invasive. The findings single out transmembrane protein CDCP1 as a promising therapeutic target for disrupting the process.

Epithelial cells, which line the surfaces and organs of the body, can protect themselves against cancer by removing unhealthy or abnormal cells through a mechanism known as apical extrusion. In this process, damaged cells are forcibly removed from the cell layer by the surrounding healthy cells.  Until a recent study published in Current Biology, however, it was unknown how cells managed to evade apical extrusion.

A research group led by Osaka University found that the location of Src within the cell membrane determined how it behaved; when Src was located inside lipid rafts—which are more ordered arrangements of lipids within the cell membrane—cancer cells were able to become invasive and overcome the protective mechanisms of the normal cell layer.

The Osaka team also showed that another molecule, known as CDCP1, controls the location of Src by forming molecular scaffolds that activate it. “By analyzing cancer cells, we showed that CDCP1 promoted cancer cell invasion, while inhibition of CDCP1 led to the elimination of the cancerous cells by apical extrusion,” says lead author Kentaro Kajiwara, with the University’s Department of Oncogene Research.

CDCP1 recruitment of Src to lipid rafts triggers a cascade that ultimately results in cancer cells escaping apical extrusion by invading the basal layer. This initial recruitment step is vital to the process. “The spatial control of Src activation by CDCP1 in lipid rafts is vital to convey resistance to the process of apical extrusion and allows the cancerous cells to become invasive, promoting carcinogenesis,” explains senior author Masato Okada.

The expression of CDCP1 is already known to be increased in certain types of cancers, such as lung and pancreatic cancer and this work provides mechanistic insight into its roles in cancer cell invasion. The study also shows that CDCP1 could be a promising target of drug treatment for early-stage cancers.