The tumor-promoting functions of Ataxia-telangiectasia mutated (ATM) in cancer cells

Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression by protecting cells from DNA double-strand breaks (DSBs). However, how ATM functions outside of DSB signaling is less clearly understood. Here, we report a new cancer-promoting role for ATM in stimulating cell migration and invasion independently of DSB signaling or induction. We used two highly metastatic human breast cancer cell lines to corroborate that ATM is required for cell migration and invasion. Microarray analysis of cells depleted for ATM identified interleukin-8 (IL-8) as a target since the exogenous addition of IL-8 rescued migration and invasion defects in ATM-deficient cells. Finally, ATM depletion in human cancer cells reduced lung metastasis in a mouse xenograft model. These findings shed light on tumor-promoting functions of ATM. Therefore, in addition to its canonical roles in tumor suppression, ATM promotes tumor progression as well.