ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion

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Abstract

Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

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Chen, W. T., Ebelt, N. D., Stracker, T. H., Xhemalce, B., Van Den Berg, C. L., & Miller, K. M. (2015). ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion. ELife, 4(JUNE). https://doi.org/10.7554/eLife.07270

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