Genome-Wide RNAi Screen Identifies PMPCB as a Therapeutic Vulnerability in EpCAM⁺ Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a genetically heterogeneous disease for which a dominant actionable molecular driver has not been identified. Patients with the stem cell-like EpCAM⁺AFP⁺ HCC subtype have poor prognosis. Here, we performed a genome-wide RNAi screen to identify genes with a synthetic lethal interaction with EpCAM as a potential therapeutic target for the EpCAM⁺AFP⁺ HCC subtype. We identified 26 candidate genes linked to EpCAM/Wnt/β-catenin signaling and HCC cell growth. We further characterized the top candidate PMPCB, which plays a role in mitochondrial protein processing, as a bona fide target for EpCAM⁺ HCC. PMPCB blockage suppressed EpCAM expression and Wnt/β-catenin signaling via mitochondria-related reactiv

SUBMITTER: Takai A 

PROVIDER: S-EPMC6497533 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature