Background Adherent junction associated protein 1 (AJAP1), a typical molecule of adherent junctions, has been found to be a tumor suppressor in many cancer types. Aberrant activation of β-catenin has been demonstrated to be associated with malignant biological properties of tumors including breast cancer. This study aimed to investigate the function and mechanism of AJAP1-mediated β-catenin activity of breast cancer lines in vitro and in breast cancer patients. Methods AJAP1 and β-catenin expressions in breast cancer tissues and cell lines were detected by immunohistochemistry, western blotting and qRT-PCR. The EGF/EGFR axis-mediated AJAP1 attenuated β-catenin nuclear location was measured by western blotting, immunofluorescence assay, co-immunoprecipitation, luciferase assay and ubiquitination assays. Furthermore, the function of AJAP1 and β-catenin regulated breast cancer progression was explored both in vivo and in vitro . Results It was found that AJAP1 had a high negative correlation with β-catenin nuclear expression and was a novel tumor suppressor in breast cancer. AJAP1 loss can mediate β-catenin accumulated in cytoplasm and then transferred it to the nucleus, activating β-catenin transcriptional activity and downstream genes. Additionally, β-catenin can reverse the invasion, proliferation ability and tumorigenicity of the depletion of AJAP1 caused both in vivo and in vitro. Besides, EGF/EGFR also involved in the process of AJAP1-depiction induced β-catenin transactivation to the nucleus. More importantly, EGFR depletion/AJAP1 knocked down promoted the progression of breast cancer by regulating the activity of β-catenin nuclear transactivation. Conclusion This study demonstrated that AJAP1 acted as a putative tumor suppressor while β-catenin nuclear localization positively fed back on EGF/EGFR-attenuated AJAP1 expression in breast cancer, which might be beneficial to develop new therapeutic targets for decreasing nuclear β-catenin-mediated malignancy in breast cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1252-6) contains supplementary material, which is available to authorized users.

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BackgroundThe most striking feature of molecular apocrine breast cancer (MABC) is the expression of androgen receptor (AR). We report here the mechanism of the AR in regulating the behavior of MABC.MethodsThe MABC cell line, MDA-MB-453, and the nonMABC cell line, MCF7, were used in this study. The effect of dihydrotestosterone (DHT) and heat shock protein 27 (HSP27) on cell proliferation was quantified using the cell counter kit-8 (CCK8) and clonogenic assays in vitro and by a xenograft tumor model in vivo. The expression of the AR and HSP27 was analyzed using western blot, qPCR, and immunofluorescence assays. Complexes of the AR and HSP27 were detected by co-immunoprecipitation (Co-IP).ResultsIn MDA-MB-453 cells, DHT promoted cell proliferation and stimulated AR and HSP27 translocation from the cytoplasm to the nucleus, whereas, it inhibited MCF7 cell growth, and only the AR translocated into the nucleus. HSP27 knock-down decreased the proliferative ability of MDA-MB-453 cells, which could be rescued by DHT, while HSP27 and DHT had synergistic effects on MCF7 cells. HSP27 phosphorylation was a prerequisite for AR translocation into the nucleus, especially phosphorylation on serine 82. In addition, DHT stimulated the tumorigenic and metastatic capacities of MDA-MB-453 cells, while HSP27 knock-down decreased the rate of tumor formation and induced apoptosis in cells.ConclusionsThe results suggest that HSP27 assists the AR in regulating the malignant behavior of MABC, and these findings might be helpful in the treatment of MABC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0762-y) contains supplementary material, which is available to authorized users.

BackgroundAndrogen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear.MethodsAR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR–PDEF–MAD1–MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo.ResultsWe found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo.ConclusionsOur data highlight the role of the AR–PDEF–MAD1–MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0883-0) contains supplementary material, which is available to authorized users.

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