SLC7A5 serves as a prognostic factor of breast cancer and promotes cell proliferation through activating AKT/mTORC1 signaling pathway

Background: The purpose of our research was to determine if the clinical, pathological, and prognostic functions of SLC7A5 are the same as those of other molecular breast cancer (BC) subgroups. Methods: We used the Oncomine and The Cancer Genome Atlas (TCGA) online databases to examine the expression and genetic changes of SLC7A5 in BC tissues. Immunohistochemical analysis was used to validate the SLC7A5 protein expression in subtypes of BC, while Kaplan-Meier figures and log-rank tests were used to evaluate the prognostic relevance of SLC7A5. Uni- and multivariate Cox regression models were adapted to analyze hazard ratios (HRs) and the independent prognostic factors. We analyzed the alterations of different malignancies of luminal cells by up-regulation of SLC7A5 in human luminal cell lines MCF-7. SLC7A5 was overexpressed in luminal cells, and then the AKT, mTOR, and p70-S6K phosphorylation and expression were analyzed by western blot analysis and real-time quantitative polymerase chain reaction (qPCR). Results: Our results suggested that SLC7A5 was overexpressed in BC cell lines and in patients' tissues. Elevated SLC7A5 messenger RNA (mRNA) and SLC7A5 protein expression was correlated to a worse clinical prognosis (P<0.001) in luminal subtypes of BC. The multivariate analysis suggested that high level of SLC7A5 expression could be an independent prognostic factor for decreased overall survival (OS). The study also demonstrated that SLC7A5 overexpression increased proliferation of MCF-7 cells by reducing the cell cycle arrest in G1 phase. Our mechanistic study further indicates that SLC7A5 enhances the proliferation of the MCF-7 cell by activation of AKT/mTORC1 pathway through phosphorylation. Conclusions: Our study demonstrated that SLC7A5 may have a vital function in the biology of BC cells, indicating that SLC7A5 is a potential prognostic biomarker and may be a valuable therapeutic target in BC patients.