FAM117B Promotes Colorectal Cancer Progression by Enhancing DYRK1A-mediated Phosphorylation of PLK2.

Among solid tumors, colorectal cancer (CRC) ranks as one of the most frequently diagnosed. This study aimed to investigate the role and underlying mechanism of family with sequence similarity 117 member B (FAM117B) in CRC. Western blotting was applied to detect FAM117B levels in both human normal colorectal epithelial cells and CRC cells. The malignant capabilities of CRC cells were assessed using flow cytometry, colony formation assays, and Transwell assays. In vivo, subcutaneous tumorigenesis and splenic-to-liver metastasis models were established in nude mice by injecting CRC cells. The effects of FAM117B knockdown on CRC subcutaneous tumor growth and liver metastasis were evaluated. Co-immunoprecipitation (Co-IP) and immunoprecipitation (IP) were employed to examine the FAM117B-dual specificity tyrosine (Y)-Regulated Kinase 1 A (DYRK1A) interaction, as well as the effect of DYRK1A on Polo-like kinase 2 (PLK2) phosphorylation. Cellular experiments demonstrated elevated FAM117B expression in CRC. Knockdown of FAM117B attenuated CRC cell proliferation, migration, and invasion. In vivo, FAM117B knockdown diminished CRC tumor growth and liver metastasis. A specific interaction exists between FAM117B and DYRK1A, with FAM117B acting as an upstream regulator of DYRK1A. Furthermore, DYRK1A induced PLK2 phosphorylation in CRC cells, thereby upregulating PLK2 protein expression. DYRK1A overexpression reversed the inhibitory effects of FAM117B inhibition on CRC cell malignancy. Conversely, PLK2 knockdown counteracted the effects mediated by DYRK1A overexpression. In conclusion, FAM117B promoted the pathological progression of CRC through enhancing the DYRK1A/PLK2 signaling pathway. Our study provided insights for potential therapeutic strategies against CRC.