Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy.

Yvonne Xinyi Lim, Hexian Lin, Sock Hong Seah, Yoon Pin Lim

Cells 2021 Nov 11

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Cancer is a global health problem. The delineation of molecular mechanisms pertinent to cancer initiation and development has spurred cancer therapy in the form of precision medicine. The Hippo signalling pathway is a tumour suppressor pathway implicated in a multitude of cancers. Elucidation of the Hippo pathway has revealed an increasing number of regulators that are implicated, some being potential therapeutic targets for cancer interventions. WW domain-binding protein 2 (WBP2) is an oncogenic transcriptional co-factor that interacts, amongst others, with two other transcriptional co-activators, YAP and TAZ, in the Hippo pathway. WBP2 was recently discovered to modulate the upstream Hippo signalling components by associating with LATS2 and WWC3. Exacerbating the complexity of the WBP2/Hippo network, WBP2 itself is reciprocally regulated by Hippo-mediated microRNA biogenesis, contributing to a positive feedback loop that further drives carcinogenesis. Here, we summarise the biological mechanisms of WBP2/Hippo reciprocal regulation and propose therapeutic strategies to overcome Hippo defects in cancers through targeting WBP2.

Citation

Yvonne Xinyi Lim, Hexian Lin, Sock Hong Seah, Yoon Pin Lim. Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy. Cells. 2021 Nov 11;10(11)