The Functional Study of S100A11 in Triple Negative Breast Cancer

Abstract

Triple negative breast cancer (TNBC) is the most aggressive subtype of this disease, accounting for approximately 15% of all breast cancers. Moreover, the prognosis of patients with this subtype is exacerbated by its high metastasis and recurrence rates, as well as drug resistance. However, treatments are limited owing to a lack of suitable receptors to target. In this study, I performed transcriptome profiling for breast cancer and TNBC based on reference to the Gene Expression Omnibus (GEO) database. I found evidence to indicate that S100 calcium-binding protein A11 (S100A11) is a potential therapeutic target. S100A11 is an S100A protein that regulates enzyme activity and several cellular mechanisms in response to calcium ions. Although S100A11 has been extensively studied in the field of cancer research as a tumor-promoting factor, there has to date been no research conducted on this protein in the context of breast cancer. During the course of this study, I validated the functionality of S100A11 based on analyses of in silico data, patient samples, and breast cancer cell lines. Data retrieved from the TCGA database revealed S100A11 to be highly expressed in patients with breast cancer. Analysis of patient samples indicated that, compared with normal tissues, S100A11 expression is upregulated in cancer tissues depending on the grade, and that expression patterns are also associated with patient prognosis. Inhibition of S100A11 was found to promote a significant increase in cell death, particularly in TNBC cell lines. Furthermore, the findings of western blot and RT-qPCR analyses revealed a correlation between the expression of S100A11 and that of BIM. Moreover, S100A11 knockdown-mediated AKT-FoxO3a signaling was found to activate BIM expression, and thereby induce apoptosis. On the basis of this elucidation of the mechanisms whereby S100A11 functions in TNBC, I propose S100A11 to be a novel biomarker and new therapeutic target for the treatment of TNBC.