Smoke-induced SAV1 Gene Promoter Hypermethylation Disrupts YAP Negative Feedback and Promotes Malignant Progression of Non-small Cell Lung Cancer.

ABSTRACT: YAP (gene symbol YAP1) as a potential oncoprotein, is positively correlated with the malignancy of various tumors. However, overexpression of YAP alone in multiple normal tissue cells has failed to induce tumor formation and the underlying mechanism is poorly understood. Herein, we show that YAP activation directly induces transcription of its negative regulator, SAV1, to constitute a negative feedback loop, which plays a vital role in maintaining lung epithelial cell homeostasis and was dysregulated in non-small cell lung cancer (NSCLC). Notably, smoking promotes the hypermethylation of the SAV1 promoter region, which disrupts YAP negative feedback by inactivating the Hippo pathway. Besides, exogenous overexpression of SAV1 can act as a traffic protein, activating the Hippo

SUBMITTER: Liu T 

PROVIDER: S-EPMC9295071 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature