Breast cancer is the leading cause of women death. Heat shock protein 90 (HSP90) and Histone deacetylase 6 (HDAC6) are promising anti-cancer drug targets. However, it's still unclear the applicability of anti-HSP90 and anti-HDAC6 strategies in precision treatment of breast cancer. In current study, we found that triple negative breast cancer (TNBC) cells, compared to T47D, an ERα+ breast cancer cell line, exhibited 7~40 times lower IC₅₀ values, stronger cell cycle perturbation, increased cell apoptosis and stronger inhibition of cell migration upon 17-DMAG treatment, while T47D, compared to TNBC cells, expressed higher HDAC6 and showed stronger anti-cancer response upon treatment of Tubacin. Mechanically, 17-DMAG treatment inhibited a complex network consists at least ERK, AKT, and Hippo pathway in TNBC cells, and higher expression of HDAC6 inhibited HSP90 activity via deacetylating HSP90. Furthermore, we found higher HDAC6 expression level in tamoxifen-resistance T47D than that in T47D, and Tubacin treatment suppressed the growth of tamoxifen-resistant cells in vivo. Our data suggested that anti-HSP90 and anti-HDAC6 are promising strategies to treat TNBC and ERα+ breast cancers respectively, and anti-HDAC6 can be considered during treatment of tamoxifen-resistance breast cancers.

Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1 recognizes both gene proximal and distal transcription start site (TSS) sequences to repress gene expression. Co-IP mass spectrometry and biochemical studies showed that TRPS1 binds to CHD4/NuRD(MTA2). Genome-wide and molecular studies revealed that CHD4/NuRD(MTA2) is required for TRPS1 transcriptional repression. Mechanically, TRPS1 and CHD4/NuRD(MTA2) form precision-guided transcriptional repression machinery in which TRPS1 guides the machinery to specific target sites by recognizing GATA elements, and CHD4/NuRD(MTA2) represses the transcription of target genes. Furthermore, TP63 was identified and validated to be a direct target of TRPS1-CHD4/NuRD(MTA2) complex, which represses TP63 expression by involving decommission of TP63 enhancer in the described precision-guided manner, leading to a reduction of the ΔNp63 level and contributing to migration and invasion of cancer cells.

Background: Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single‐cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype‐associated subpopulations is challenging.Results: Here, we applied Scissor (single‐cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC‐deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer‐associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC‐deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK‐STATs signaling. FABP5+ macrophages show low antigen‐presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T‐cell immune infiltration through cell interaction in breast tumor microenvironment.Conclusion: Taken together, our study reveals survival‐associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.

Hepatocellular carcinoma (HCC) is a common malignancy in human. CD44 is a transmembrane glycoprotein which is frequently overexpressed in cancer of various origins. The function and mechanism of CD44 in HCC remains elusive. In this study, we reported that CD44 was overexpressed in HCC to promote the proliferation and migration of HCC cells via oncogenic YAP, which is the key downstream regulator in Hippo pathway. These findings suggest that CD44-YAP is a probable important axis in pathogenesis of HCC, providing an insight in to HCC pathogenesis as well as potential targets for the intervention of HCC.