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

Gloss

Vascular endothelial growth factor (VEGF) is essential for angiogenesis, which not only promotes the vascularization of organs during development but also fuels the growth of tumors. Independently of its angiogenic effects in endothelial cells, VEGF signaling within tumor cells is associated with the acquisition of stem cell–like traits that are associated with drug resistance and metastasis. However, targeting VEGF receptors has had limited therapeutic efficacy. In this Review, which contains one figure and 60 references, we discuss how YAP and TAZ, transcriptional effectors in the Hippo pathway, transduce VEGF signals into transcriptional and cytoskeletal alterations that promote both angiogenesis and the acquisition of stem-like traits in tumor cells.

Abstract

Vascular endothelial growth factor (VEGF) stimulates endothelial cells to promote both developmental and pathological angiogenesis. VEGF also directly affects tumor cells and is associated with the initiation, progression, and recurrence of tumors, as well as the emergence and maintenance of cancer stem cells (CSCs). Studies have uncovered the importance of the transcriptional regulators YAP and TAZ in mediating VEGF signaling. For example, VEGF stimulates the GTPase activity of Rho family members and thereby alters cytoskeletal dynamics, which contributes to the activation of YAP and TAZ. In turn, YAP- and TAZ-mediated changes in gene expression sustain Rho family member activity and cytoskeletal effects to promote both vascular growth and remodeling in endothelial cells and the acquisition of stem-like traits in tumor cells. In this Review, we discuss how these findings further explain the pathophysiological roles of VEGF and YAP/TAZ, identify their connections to other receptor-mediated pathways, and reveal ways of therapeutically targeting their convergent signals in patients.

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