Colorectal cancer stem cells (CSCs) serve crucial functions in tumor relapse, metastasis and therapy failure. Interleukin 17 receptor A (IL-17RA) is a potent mediator in the pathogenesis and progression of colorectal cancer. Our previous study showed that IL-17RA could promote angiogenesis, tumor growth and metastasis. In addition, IL-17RA was correlated with CRC recurrence. Recent study showed IL-17RA play a potential role in self-renewal in glioma stem cells. This study aims to evaluate the functional role and mechanism of IL-17RA in colorectal CSCs.
In this study, IL-17RA stable overexpression cells were used to examine the change of sphere formation, proliferation, CSC markers and epithelial-mesenchymal transition biomarkers and the regulation mechanism of signaling pathway. The specific IL-17RA signaling inhibitors were used to evaluate the function of the IL-17RA signaling affecting the CSC markers, epithelial-mesenchymal transition gene expression and sphere formation.
We observed high IL-17RA expression can significantly promote the self-renewal by increasing stem cell markers CD133, ALDH1, Lgr5 and Sox2 expression and the ability to form tumorsphere in SW480 and SW620 cells. In additional, IL-17RA overexpression markedly increased chemoresistant ability and mesenchymal markers Vimentin, Slug, Snail, Zeb1expression. The STAT3 inhibitor remarkably decreased the CD133 stem cell gene, drug resistance and tumorsphere ability.
IL-17RA can enhance the self-renewal ability via activating the STAT3 pathway. Therefore, we expect that IL-17RA could serves as a prognosis marker and a potential therapeutic target in CRC.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
All authors have declared no conflicts of interest.