Interaction And Regulatory Mechanism Of HSP90-HDAC6 In Different Subtypes Of Breast Cancer

Breast cancer is one of the malignant tumors that threaten global women's health.The incidence of breast cancer is increasing with years.With the improvement of medical treatment,the mortality is effectively controlled but still accounts for nearly 1/3 of the disease.Lacking of therapeutic targets for triple-negative breast cancer(TNBC)and resistance problems of anti-non-triple negative breast cancer(non-TNBC)targeted drugs,are the two formidable challenges facing the clinical therapy.Heat shock protein 90(HSP90)is a kind of molecular chaperones that rely on ATP and play an important role in the process of cell protein synthesis,folding,stable configurations,correct assembly,transportation and degradation,HSP90 and histone deacetylase 6(HDAC6)forming regulatory network is postulated to be the potential target of anti-cancer drugs.As acknowledged,the Hippo pathway plays a pivotal role in cancer development.In current study,TNBC and non-TNBC cells were treated with 17-DMAG and Tubacin,the inhibitors of HSP90 and HDAC6.Cell proliferation assay,wound healing assay,in vitro migration,cell cycle and apoptosis assays were used to detect the sensitivity of breast cancer cells to the inhibitors.The functional mechanism of the inhibitors on the biological behavior of breast cancer cells was investigated by Western blot,immunofluorescence assay and Real-time Quantitative PCR,etc.We found that TNBC cells have higher sensitivity to 17-DMAG treatment compared to non-TNBC cells,Hippo pathway and ERK,AKT signaling pathway crosstalk in HSP90 regulating network;non-TNBC cells are relatively insensitive towards 17-DMAQ but respond to Tubacin,HSP90 may be highly actived after deacetylated by HDAC6 to be relatively insensitive to its inhibitors.Our data strongly suggests that Hippo pathway is involved in HSP90-HDAC6 regulatory network and provides a new strategy for precise treatment in breast cancer.