LukS-PV targeting C5aR inhibits EMT in hepatocellular carcinoma via the BCL6/HDAC6/HSPD1 axis.

ABSTRACT: Hepatocellular carcinoma (HCC) is a highly lethal malignancy, with epithelial-mesenchymal transition (EMT)-driven metastasis a key factor for poor prognosis. The C5a/C5a receptor (C5aR) pathway significantly facilitates HCC cell EMT, yet no approved anti-cancer drugs specifically target C5aR. LukS-PV, a component of Staphylococcus aureus-secreted Panton-Valentine leukocidin (PVL), specifically targets C5aR and exerts anti-tumor effects in hematological and solid tumors. However, its impact on HCC EMT and mechanisms remains unknown. Our study showed LukS-PV targets C5aR to inhibit HCC cell EMT, migration, invasion, and in vivo lung metastasis. Mechanistically, LukS-PV downregulates B-cell lymphoma 6 (BCL6), reducing histone deacetylase 6 (HDAC6) expression. Decreased HDAC6 increases heat sh

SUBMITTER: Ding P 

PROVIDER: S-EPMC12936196 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature