JCI paper implicates the FAK gene in cellular functions like proliferation, survival, and avoidance of senescence.

Memorial Sloan-Kettering Cancer Center researchers say that they have new insight into the initiation, maintenance, and progression to metastasis of a specific subset of human and mouse breast cancers. They noticed that the focal adhesion kinase (FAK) gene, a core component of integrin signaling, was amplified and that FAK mRNA was often overexpressed.

A marked proportion of breast cancers are associated with excessive activation of either the protein Ras or PI3K signaling pathways. In this study, investigators found that silencing the FAK gene arrested the growth of human breast cancer cells with excessive activation of either Ras or PI3K signaling pathways. They therefore propose that combined inhibition of FAK and either PI3K or Ras signaling may provide an effective approach for the treatment of breast cancer.

A mammary gland–specific deletion of FAK in mice did not seem to affect normal mammary epithelial cells, and these mice were protected from tumors initiated by the polyoma middle T oncoprotein (PyMT), which activates Ras and PI3K. FAK-deficient PyMT-transformed cells showed arrested growth and apoptosis as well as diminished invasive and metastatic capacity.

The team concludes that elimination of FAK does not clearly affect mammary gland development but it suppresses tumor initiation and progression in the PyMT model of breast cancer. In cell culture, FAK does not appear to be necessary for normal cell survival and proliferation. It does, however, support Ras- and PI3K-dependent neoplastic transformation by facilitating multiple core functions including proliferation, survival, and avoidance of senescence. In addition, FAK is necessary for tumor invasion and metastasis.

This article appeared online in the Journal of Clinical Investigation on January 19.

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