VEGF–neuropilin-2 signaling promotes stem-like traits in breast cancer cells by TAZ-mediated repression of the Rac GAP β2-chimaerin

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Science Signaling  01 May 2018:
Vol. 11, Issue 528, eaao6897
DOI: 10.1126/scisignal.aao6897

A Rac-TAZ loop drives cancer stem cells

In various cancers, stem-like cells called CSCs may drive tumor growth, metastasis, recurrence, and drug resistance; thus, blocking the survival and proliferation of CSCs may enhance the efficacy of anticancer therapies in patients. Elaimy et al. found that CSC phenotypes in breast cancer cells are supported by VEGF, a growth factor that is associated with poor prognosis in breast cancer patients. Through its receptor NRP2 and subsequent activation of the kinase FAK and the protein Rac1, VEGF activated the Hippo pathway transcription cofactor TAZ, which bound and repressed the promoter of the gene encoding the enzyme β2-chimaerin. β2-chimaerin effectively shuts off Rac1; thus, its loss promoted sustained Rac1 activity in a self-perpetuating loop that promoted CSC-like behavior in cells and correlated with stem-like and metastatic markers in patient tumors.

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