RESUMO
Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.
RESUMO
Objective To investigate the role of HBXIP overexpression in the prognostic evaluation of breast cancer. Methods HBXIP expression was detected in the tissues of 60 breast cancer cases and 15 cases of ductal cancer in situ (DCIS) as well as in the adjacent non-tumorous tissues of 27 cases of breast cancer using EnVision immunohistochemical staining method. The correlations between the HBXIP overexpressions and the clinical pathological characters of the patients with breast cancer were also analyzed. Results The HBXIP proteins showed a major cytoplasmic staining pattern in breast cancer. The strongly positive rate of HBXIP was75.0%(45/60) in breast cancer, significantly higher than in DCIS (20.0%, 3/15) and adjacent non-tumorous tissues (14.8%, 4/27). High-level expression of HBXIP was correlated with late clinical stage, lymph node metastasis and HER-2 positive expression in breast cancer. Conclusions The expression level of HBXIP is closely related to the progression and prognosis of breast cancer. It might be a potential biomarker and therapeutic target of breast cancer.
RESUMO
Objective To investigate the expressions of HBXIP and GRIM-19 in hepatocellular carcinoma tissues and their clinic significance. Methods Hepatocellular carcinoma tissue (n=42) and normal liver tissue (n=28) were collected from Tianjin First Central Hospital,immunohistochemistry was used to detect the expressions of HBXIP and GRIM-19 in these two groups. Results Rate of cells with positive expressions of HBXIP in hepatocellular carcinoma and normal liver tissues were 80.95%(34/42)and 42.86%(12/28)respectively;Rate of cells with positive expression of GRIM-19 in hepato?cellular carcinoma tissues and normal liver tissues was 40.48%(17/42)and 75.00%(21/28)respectively, and the difference between these two groups was statistically significant(P<0.05);The expression of HBXIP was higher but the expression of GRIM-19 was lower in poor differentiated and stageⅢ-IV cells than those in well and moderate differentiated cells and in stage I-II, cells. What′s more, the expression of GRIM-19 is higher in tissue without portal thrombosis than that in tissue with portal thrombosis. The expression of HBXIP was negatively correlated with GRIM-19 expression(rS=-0.400,P<0.01). Conclusion The abnormal expressions of HBXIP and GRIM-19 may play important roles in the process of development and metastasis of hepatocellular carcinoma.