Loss of HCRP1 leads to upregulation of PD-L1 via STAT3 activation and is of prognostic significance in EGFR-dependent cancer

Loss of hepatocellular carcinoma-related protein 1 (HCRP1) (alias VPS37A) plays a role in endocytosis receptor tyrosine kinases as member the ESCRT complex and has been linked to poor patient outcome various types epithelial cancer. To this date, molecular biological mechanisms explaining how its absence would contribute tumor progression remain unknown. Using genomic editing with CRISPR-Cas9, we generated ovarian breast cancer cell lines loss-of-function mutations HCRP1. We hypothesized that pathways downstream such epidermal growth factor are affected by HCRP1 loss looked for deregulated signaling using immunoblotting classical biology assays. In our study, show endogenous deletion leads elevated phosphorylation transcription Signal transducer activator 3 (STAT3) induces upregulation PD-L1, an important regulator immune checkpoint inhibition. further mesenchymal phenotype switch cells, leading increased proliferation migration. Concludingly, data emphasize microenvironment tumors low or absent expression suggest potential marker metastatic immunogenicity receptor-driven AT A GLANCE COMMENTARYTomasich E, et al.BackgroundHCRP1 receptor-tyrosine through complexes is lost frequently EGFR kinase highest significance carcinomas can lead activation intracellular effectors, including STAT3.Translational SignificanceIn work, STAT3 hence STAT3-target crucial targeted novel immunotherapies. Biomarkers predicting response these therapies dearly needed. Our propose marker. Tomasich al. STAT3.