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An overview of the crosstalk between YAP and cGAS-STING signaling in non-small cell lung cancer: it takes two to tango

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Abstract

The cyclic GMP-AMP synthase (cGAS)—stimulator of interferon genes (STING) pathway is recognized as a main mediator bridging innate and adaptive immunity, recent advances have expanded its roles to anti-tumor immunity and carcinogenesis. Loss of cGAS-STING signaling in non-small cell lung cancer (NSCLC) leads to enhanced tumorigenicity and decreased cytotoxic T lymphocyte infiltration. Apart from its anticancer response, persistent overreaction of cGAS-STING signaling promotes progression of certain inflammation-aggravated cancers. Activation of the pro-inflammatory nucleic acid sensing pathway can trigger Hippo pathway, which mediates the inactivation of Yes-associated protein 1 (YAP1) and its paralogue transcriptional co-regulators with PDZ-binding motif (TAZ, also known as WWTR1), and subsequent suppression of tumorigenesis. Active YAP acts as a transcriptional driver in bolstering immunosuppressive cytokines to evade immune surveillance and promote occurrence of preneoplasia. It is reasonable that aggressive tumors co-opt these regulators to generate few immunogenic antigens and drive tumorigenic behaviors via a highly cooperative manner. Given their multifaced roles, we profile the molecular biology characteristic and current status underpinning oncogenic YAP, review its crosstalk roles with cGAS/STING pathway in NSCLC, and summarize the major clinical investigations in NSCLC with TCGA database.

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  1. Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China

    Fang Hao

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Hao, F. An overview of the crosstalk between YAP and cGAS-STING signaling in non-small cell lung cancer: it takes two to tango. Clin Transl Oncol 24, 1661–1672 (2022). https://doi.org/10.1007/s12094-022-02826-7

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