Research ArticleCancer

Signaling from mTOR to eIF2α mediates cell migration in response to the chemotherapeutic doxorubicin

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Science Signaling  17 Dec 2019:
Vol. 12, Issue 612, eaaw6763
DOI: 10.1126/scisignal.aaw6763

Moved by DNA damage

Doxorubicin is a commonly used therapeutic that kills cancer cells by inducing genotoxic stress. Harvey et al. found that, at clinically relevant doses, doxorubicin promoted cancer cell migration. Doxorubicin inhibited the multiprotein complex mTORC1, which led to the phosphorylation of the translation factor eIF2α. This phosphorylation event would normally be expected to inhibit protein synthesis, but instead, it led to increased migration of doxorubicin-treated cancer cells. Inhibiting eIF2α phosphorylation with an FDA-approved drug restricted doxorubicin-induced cell migration. These results suggest that although inhibiting mTORC1 may shut down protein synthesis in tumors, it may enhance metastasis in response to doxorubicin.

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