PPP1CA promotes hepatocellular carcinoma progression in a YAP1-dependent way

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-06-11 DOI:10.1016/j.cellsig.2025.111938

Xing Liu , Guangxi Xu , Weiming Luo , Kaisheng Wang , Feitong Wang

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Abstract

Hepatocellular carcinoma (HCC) exhibits high incidence, malignancy, and mortality rates. Inactivation of the Hippo pathway has been implicated in the acquisition of malignant characteristics in HCC. The present study identifies upregulation of protein phosphatase 1 catalytic subunit alpha (PPP1CA) in HCC tissues, with elevated PPP1CA expression correlating with poor prognosis in patients with HCC. Functionally, PPP1CA acts as an oncogenic driver that facilitates cell proliferation and migration in HCC. Mechanistic investigations reveal that PPP1CA interacts with YAP1, inducing YAP1 dephosphorylation and promoting its nuclear translocation, ultimately activating transcription of Hippo pathway target oncogenes. Additionally, PPP1CA knockdown exhibits a synergistic effect with YAP1 inhibitors, significantly suppressing HCC tumor proliferation in vivo. Collectively, these findings underscore the pivotal role of PPP1CA in regulating HCC tumorigenesis through a YAP-dependent mechanism, highlighting PPP1CA as a promising therapeutic target for HCC intervention.

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PPP1CA以yap1依赖的方式促进肝细胞癌的进展

肝细胞癌（HCC）具有高发病率、恶性程度和死亡率。Hippo通路的失活与HCC恶性特征的获得有关。本研究发现蛋白磷酸酶1催化亚单位α (PPP1CA)在HCC组织中表达上调，PPP1CA表达升高与HCC患者预后不良相关。功能上，PPP1CA在HCC中作为促进细胞增殖和迁移的致癌驱动因子。机制研究表明PPP1CA与YAP1相互作用，诱导YAP1去磷酸化并促进其核易位，最终激活Hippo通路靶癌基因的转录。此外，PPP1CA敲低与YAP1抑制剂表现出协同作用，在体内显著抑制HCC肿瘤增殖。总的来说，这些发现强调了PPP1CA通过yap依赖机制在调节HCC肿瘤发生中的关键作用，强调PPP1CA是HCC干预的有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.