S100A11 is a diagnostic marker and promotes cancer progression for luminal breast cancer

Abstract

Background: S100A11, also known as calgizzarin, is a member of S100 calcium-binding protein family and is upregulated in various cancers including lung cancer, renal cell cancer, ovarian cancer and pancreatic cancer. Many studies have shown that S100A11 is related to cancer progression. However, the function of S100A11 in breast cancer remains largely unknown. In the present study, we aim to investigate the underlying mechanism(s) of S100A11 in cancer cell proliferation, invasion, migration, and evaluate the clinical association with breast cancer. Methods: The mRNA expression level of S100A11 in plasma samples from breast cancer patients and normal control individuals was detected with quantitative real-time PCR. Knockdown of S100A11 using small interfering RNA (siRNA) in luminal breast cancer cells (MCF-7 and T-47D) were used to study the biological function of S100A11 for the progression of breast cancer. Cell proliferation ability was analysed with MTT assay and colony formation assay. Cell invasion ability was analysed with transwell invasion assay. Cell migration ability was detected by wound healing assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Results: The mRNA expression level of S100A11 was significantly increased in the plasma samples obtained from 182 breast cancer patients compared with 115 normal control individuals, and the area under curve was 0.83. In particular, higher expression was associated with luminal breast cancer subtype as well as respective cell lines. S100A11 siRNA effectively inhibited the proliferation, invasion, and migration abilities of MCF-7 and T-47D cells. Knockdown of S100A11 caused cell cycle G1 arrest and induced apoptosis. Silencing of S100A11 decreased the mRNA and protein expression levels of cyclin D1 and NF-κB p50 whereas increased the expression level of E-cadherin in MCF-7 and T-47D cells. Conclusion: These results suggest that S100A11 is upregulated in breast cancer and promoted cell proliferation, invasion and migration in MCF-7 and T-47D cells through the upregulation of NF-κB p50 and cyclin D1. Thus, S100A11 may be a potential diagnostic marker for luminal breast cancer subtype and also a therapeutic target for breast cancer.