Abstract
The S100 protein family represents the largest subgroup of calcium binding EF-hand type proteins. These proteins have been reported to be involved in a wide range of biological functions that are related to normal cell development and tumorigenesis. S100A14 is a recently identified member of the S100 protein family and differentially expressed in a number of different human malignancies. However, the transcriptional regulation of S100A14 and its role in breast cancer needs to be further investigated. Here, we determined that 12-O-tetradecanoylphorbol-13-acetate (TPA) up-regulated the expression of KLF4 and facilitated its binding directly to two conserved GC-rich DNA segments within the S100A14 promoter, which is essential for the transactivation of KLF4 induced S100A14 expression. Furthermore, stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. Collectively, these results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.
Highlights
The transcriptional regulation of S100A14 and its underlying mechanism have not been fully elucidated
To explore whether the increase of S100A14 mRNA levels triggered by TPA treatment was linked to post-transcriptional regulation, we measured the half-life of S100A14 mRNA by incubating cells with actinomycin D to block de novo gene transcription
KLF4 and S100A14 Are Correlated in Breast Cancer Cell Lines and Patients, and Their Expression Levels Are of Prognostic Value for Breast Carcinoma Patient Survival—To evaluate the up-regulation of KLF4 on S100A14 expression in breast cancer, we examined the mRNA levels of KLF4 and S100A14 in breast cancer cell lines and patients
Summary
The transcriptional regulation of S100A14 and its underlying mechanism have not been fully elucidated. Stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. These results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner. S100A14 is up-regulated in basal type breast cancer and significantly associated with patient outcome (15) These results suggest that the expression and functional role of S100A14 in malignant tumors is organ-specific. KLF4 is a zinc finger protein of the Kruppel-like factor family, which are zinc finger transcription factors defined by containing a composition of three Cys2/His zinc fingers It is involved in the regulation of cell survival, proliferation, differentiation, development, and inflammation and plays significant roles in stem cell function (21–26). Analyzing gene expression profiling and clinical outcome data from published studies revealed that the expression level of S100A14 in human breast cancer is inversely correlated with metastasis-free survival, and it is significantly associated with KLF4 in both breast cancer cell lines and clinical breast cancer samples
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