PPP1CA promotes hepatocellular carcinoma progression in a YAP1-dependent way

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.

Hepatocellular carcinoma; Hippo signaling; PPP1CA; YAP1.