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A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
Published on: October 24, 2015
LukS-PV targeting C5aR inhibits EMT in hepatocellular carcinoma via the BCL6/HDAC6/HSPD1 axis
Pengsheng Ding1, Lan Shi1, Xuexue Xu2
1Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
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 shock protein 60 (HSPD1) acetylation, promoting its ubiquitin-mediated degradation and EMT inhibition. This study demonstrates LukS-PV targets C5aR to inhibit HCC EMT via the BCL6/HDAC6/HSPD1 axis, highlighting its potential as an HCC therapeutic agent. These findings provide valuable EMT regulatory insights and identify potential HCC therapeutic targets.
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