FSTL3 Promotes Tumor Cell Proliferation, Invasion, Survival and Associates with Poor Prognosis in Colorectal Cancer Patients

Abstract

Follistatin like‐3 (FSTL3) is a potent inhibitor that antagonizes TGF‐β family ligands including activin, myostatin and bone morphogenetic proteins. Though usually a secreted glycoprotein, nuclear FSTL3 expression had been noted in several cell types, suggesting the existence of specific intracellular functions of this protein. Colorectal cancer (CRC) is one of the leading malignant tumors worldwide. Its strong metastatic ability and chemoresistance tendency is a major obstacle in clinical treatment. In large cohort survival analyses, we have found that FSTL3 has a significant prognostic predictive power in colorectal cancer at both RNA and protein level. Immunohistochemistry staining of CRC specimens revealed that patients with high FSTL3 expression are significantly associated with poor survival. Our study further showed that knockdown of FSTL3 inhibited the migration and invasion of colon cancer cells and reduced tumorigenesis in vivo. Conversely, ectopic over‐expression of FSTL3 elicited the opposite effects in CRC cells. In addition, the overexpression of FSTL3 was found to confer the resistance to 5‐fluorouracil in CRC cells. mRNA profiling analyses suggested that FSTL3 drives CRC tumorigenesis through various carcinogenesis‐related pathways. Our results unveil the significance of FSTL3 in the oncogenesis of CRC, with implications for its potential use as a diagnostic or prognostic biomarker and also a candidate for therapeutic target in this disease.Support or Funding InformationThis research was supported by Academia Sinica [AS‐SUMMIT‐108].