ReviewCancer

Convergence of VEGF and YAP/TAZ signaling: Implications for angiogenesis and cancer biology

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Science Signaling  16 Oct 2018:
Vol. 11, Issue 552, eaau1165
DOI: 10.1126/scisignal.aau1165

Figures

  • Fig. 1 Schematic of VEGF and YAP/TAZ signaling thus far described in endothelial and tumor cells.

    Emerging studies suggest that VEGF signaling mediated by VEGFR2 and/or NRPs increases the activity of Rho family GTPases, resulting in LATS inhibition and YAP/TAZ activation, with consequent promotion of angiogenesis and stem cell maintenance. Integrins have a key role in this signaling by associating with NRPs and engaging the extracellular matrix (ECM). VEGF signaling can involve Src-mediated Rho activation and the consequent activation of YAP/TAZ through cytoskeletal dynamics. It can also inhibit LATS by a Rac1-dependent mechanism that involves p21-activated kinase (PAK)–mediated inhibition of Merlin. An important question is whether these two mechanisms function in concert to promote YAP/TAZ activation in response to VEGF signaling. YAP/TAZ-mediated transcription can alter the expression of genes involved in cytoskeletal remodeling and in Rho and Rac1 activation, such as through the transcriptional repression of Rac GTPase activating proteins (GAPs) that normally turn off Rac, thereby establishing a positive feedback loop.

    CREDIT: A. KITTERMAN/SCIENCE SIGNALING

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