LukS-PV inhibits hepatocellular carcinoma cells migration by downregulating HDAC6 expression

Abstract

Background Hepatocellular carcinoma (HCC) is a clinically common malignant tumor worldwide. LukS-PV is the S component of Panton-Valentine leukocidin secreted by Staphylococcus aureus, which has shown anti-cancer activity. Based on previous findings, this study investigated the effects of LukS-PV on HCC migration and the potential molecular mechanisms involving acetylation pathways. Methods After treating HCC cells with different concentrations of LukS-PV, we used scratch assays to determine the mobility of the cancer cells. Western blots were used to determine the expression levels of migration-related proteins. Quantitative proteomic sequencing was used to evaluate proteomic changes in target proteins. Immunoprecipitation and liquid chromatography coupled with tandem mass spectrometry analyses were used to validate the binding of related target proteins. Results LukS-PV inhibited HCC cell migration in a concentration-dependent manner. In addition, LukS-PV attenuated the expression of histone deacetylase (HDAC)6, which is highly expressed in HCC cells. Further studies showed that LukS-PV increased the acetylation level of α-tubulin by down-regulating HDAC6, which resulted in the inhibition of HCC cell migration. Conclusion Taken together, our data revealed a vital role of LukS-PV in suppressing HCC cell migration by down-regulating HDAC6 and increasing the acetylation level of α-tubulin.

Interactions of Histone Deacetylase 6 with DNA Damage Repair Factors Strengthen its Utility as a Combination Drug Target in High-Grade Serous Ovarian Cancer

“…Among the significant proteins was the previously known HDAC6 substrate tubulin (TUBG1, TUBB6, TUBB3, and TUBA1C) (Table S3). Tubulin was only identified as significant in the CD2 mutant pull-down, which aligns with previous studies. − The CD1/2 double mutant condition resulted in the identification of 82 significant proteins (L1) (Figure B, Table S4). Of the 256 significant proteins in the CD1 condition, 32 overlapped with the CD2 condition (Figure C).…”

Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance

“…The NES might be responsible for the cytoplasmic localization of HDAC6. HDAC6 catalyzes the removal of acetyl groups from various cytoplasmic proteins [ 8 ] and contains a ubiquitin binding domain necessary for targeting misfolded and damaged proteins to autophagosomes for removal ( Figure 1 ). HDAC6 also contains a dynein motor biding domain necessary for aggresome formation for autophagic clearance ( Figure 1 ).…”