FNDC1 Facilitates Proliferation, Migration, and Invasion of Breast Cancer Cells Through Modulating Wnt/β-Catenin Pathway

Breast cancer is the most common malignant cancer and the leading fatal cancer in women around the world. Fibronectin type III domain-containing protein 1 (FNDC1) has been demonstrated to play crucial roles in various tumors. However, the function of FNDC1 in breast cancer remains to be addressed. Increased FNDC1 expression was found in breast cancer that is associated with individual cancer stages and lymph node metastasis through UALCAN analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays indicated that FNDC1 expression was up-regulated in breast cancer cells. The results of Cell Counting Kit-8 and colony formation assays indicated that FNDC1 promoted the proliferation of breast cancer cells. Moreover, FNDC1 knockdown suppressed xenograft tumor growth and inhibited the levels of FNDC1 and marker of proliferation Ki-67. Transwell assay demonstrated that FNDC1 promoted the migration and invasion of breast cancer cells. Importantly, mechanism analysis implied that FNDC1 promoted the Wnt/beta-catenin signaling pathway. Notably, Wnt/beta-catenin activation with LiCl significantly enhanced the proliferation and epithelial-mesenchymal transformation (EMT) inhibition effect of silencing FNDC1, whereas Wnt/beta-catenin inhibition with XAV-939 significantly weakened the proliferation and EMT promotion effect of FNDC1. Analysis of beta-catenin expression in the nucleus and cytoplasm showed that FNDC1 promoted beta-catenin nuclear translocation. These data suggested that FNDC1 exerts its oncogene function through modulating Wnt/beta-catenin signaling pathway. In conclusion, FNDC1 promotes cell proliferation, migration, invasion, and EMT through modulating Wnt/beta-catenin signaling pathway in breast cancer, providing a new idea for the development of breast cancer therapeutic targets.