EMT allows a polarized epithelium to lose epithelial integrity and acquire mesenchymal characteristics. Previously, we found that overexpression of the intracellular domain of Notch3 (N3ICD) can inhibit EMT in breast cancer cells. In this study, we aimed to elucidate the influence of N3ICD or N3ICD combined with the transmembrane domain (TD+N3ICD) on the expression and distribution of TJs/AJs and polar molecules. We found that although N3ICD can upregulate the expression levels of the above-mentioned molecules, TD+N3ICD can inhibit EMT more effectively than N3ICD alone. TD+N3ICD overexpression upregulated the expression of endogenous full-length Notch3 and contributed to correcting the position of TJs/AJs molecules and better acinar structures formation. Co-immunoprecipitation results showed that the upregulated endogenous full-length Notch3 could physically interact with E-ca in MDA-MB-231/pCMV-(TD+N3ICD) cells. Collectively, our data indicate that overexpression of TD+N3ICD can effectively inhibit EMT, resulting in better positioning of TJs/AJs molecules and cell-cell adhesion in breast cancer cells. Abbreviations : EMT: Epithelial-mesenchymal transition; TJs: Tight junctions; AJs: Adherens junctions; aPKC: Atypical protein kinase C; Crb: Crumbs; Lgl: Lethal (2) giant larvae; LLGL2: lethal giant larvae homolog 2; PAR: Partitioning defective; PATJ: Pals1-associated TJ protein

BackgroundEphAs are a class of ephrin receptors that belong to the membrane-bound receptor tyrosine kinases group. Accumulating experimental evidence has shown that the EphA family is involved in tumor progression, namely in cell proliferation, invasiveness, and metastasis. EphAs are a promising target for anticancer therapy. However, their role in breast cancer (BC) is still not well understood.Materials and MethodsWe used a series of bioinformatic approaches to analyze the expression of the EphA family members and investigate their prognostic value in BC.ResultsLower expression levels of EphA2, EphA3, EphA4, EphA5, and EphA7 and higher expression levels of EphA10 were found in BC tissues compared to those in normal tissues. The expression levels of the EphA family genes were correlated with molecular subtyping but not with tumor stage. High expression levels of most EphAs indicated a better prognosis in BC.ConclusionsThis study suggested that EphA2, EphA3, EphA4, and EphA5 can act as tumor-inhibiting factors as well as biomarkers for the prognosis of BC.

Breast cancer (BC) is an aggressive cancer with a high percentage recurrence and metastasis. As one of the most common distant metastasis organ in BC, lung metastasis has a worse prognosis than that of liver and bone. Therefore, it’s important to explore some potential prognostic markers associated with the lung metastasis in BC for preventive treatment. In this study, transcriptomic data and clinical information of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Co-expression modules constructed by weighted gene co-expression network analysis (WGCNA) found the royal blue module was significantly associated with lung metastasis in BC. Then, co-expression genes of this module were analyzed for functional enrichment. Furthermore, the prognostic value of these genes was assessed by GEPIA Database and Kaplan-Meier Plotter. Results showed that the hub genes, LMNB and CDC20, were up-regulated in BC and had a worse survival of the patients. Therefore, we speculate that these two genes play crucial roles in the process of lung metastasis in BC, which can be used as potential prognostic markers in lung metastasis of BC. Collectively, our study identified two potential key genes in the lung metastasis of BC, which might be applied as the prognostic markers of the precise treatment in breast cancer with lung metastasis.

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