S100A14 inhibits cell growth and epithelial-mesenchymal transition (EMT) in prostate cancer through FAT1-mediated Hippo signaling pathway

Abstract

Prostate cancer (PCA) is an epithelial malignant tumor occurring in the prostate gland. It is the second most common male cancer in the world and one of the top five cancer deaths in men. To combat this disease, it is needed to identify important tumor suppressor genes and elucidate the molecular mechanisms. S100 calcium-binding protein A14 (S100A14), a member of the S100 family, is located on chromosome 1q21.3 and contains an EF-hand motif that binds calcium. S100A14 is involved in a variety of tumor biological processes in several types of cancers. Its expression level and related biological functions are tissue or tumor specific. However, its possible effects on prostate cancer are still unclear. Herein, we found the low expression of S100A14 in human prostate cancer tissues and cell lines. S100A14 suppressed the proliferation of prostate cancer cells and promoted cell apoptosis. Additionally, S100A14 suppressed the motility and EMT processes of prostate cancer cells. We further found S100A14 promoted the expression of FAT1 and activated the Hippo pathway, which, therefore, suppressed the prostate cancer progression. The in vivo assays confirmed that S100A14 suppressed tumor growth of prostate cancer cells through FAT1-mediated Hippo pathway in mice. In conclusion, we clarified the mechanism underlying S100A14 suppressing prostate cancer progression and, therefore, we thought S100A14 could serve as a tumor suppressor protein.

Keywords: FAT1; Hippo pathway; Prostate cancer; S100 calcium-binding protein A14 (S100A14); Tumor suppressor.