How cancer cells spread

Researchers have found a signaling pathway in cancer cells that controls their ability to invade nearby tissues in a finely orchestrated manner.

To migrate from a primary tumor, a cancer cell must first break through surrounding connective tissue known as the extracellular matrix (ECM). The cancer cell does so by forming short-lived invadopodia--foot-like protrusions these cells use to invade.

Invadopodia release enzymes that degrade the ECM, while other protrusions pull the cancer cell along, much like a locomotive pulls a train. The invading cancer cell relies on the cycle of invadopodium formation/disappearance to successfully travel from the tumor and enter nearby blood vessels to be carried to distant parts of the body.

Study leader Louis Hodgson, Ph.D., assistant professor of anatomy and structural biology at Einstein, said they've known for some time that invadopodia are driven by protein filaments called actin, adding but exactly what was regulating the actin in invadopodia was not clear.

Using this biosensor in highly invasive breast cancer cells taken from rodents and humans, the Einstein team discovered that when an individual invadopodium forms and is actively degrading the ECM, its Rac1 levels are low; on the other hand, elevated Rac1 levels coincide with the invadopodium's disappearance.

"So high levels of Rac1 induce the disappearance of ECM-degrading invadopodia, while low levels allow them to stay-which is the complete opposite of what Rac1 was thought to be doing in invadopodia," said Dr. Hodgson.

To confirm this observation, the researchers used siRNAs (molecules that silence gene expression) to turn off the RAC1 gene, which synthesizes Rac1 protein. When the gene was silenced, ECM degradation increased. Conversely, when Rac1 activity was enhanced-using light to activate a form of the Rac1 protein-the invadopodia disappeared.

The study has been published online in the journal Nature Cell Biology.