Fndc1, or fibronectin type III domain containing 1, is a gene with diverse functions. It has been identified as a myokine, playing a crucial role in myogenesis and muscle regeneration. Mechanistically, it binds to integrin α5β1 and activates the downstream FAK/PI3K/AKT/mTOR pathway to promote myogenic differentiation [1].

In functional studies, knockdown of Fndc1 in myoblasts reduces myotube formation, while overexpression promotes myogenic differentiation. In adult mice, gain-and loss-of-function studies show that FNDC1 promotes cardiotoxin-induced muscle regeneration. Recombinant FNDC1 treatment also ameliorates pathological muscle phenotypes in the mdx mouse model of Duchenne muscular dystrophy [1].

In cancer-related research, in colorectal cancer, up-regulated FNDC1 accelerates stemness and chemoradiation resistance, and its inhibition sensitizes CRC cells to chemoradiation [2]. In lung adenocarcinoma, high expression of FNDC1 protein is associated with a shorter overall survival time, advanced clinical stage, T stage and N stage, and is an independent risk factor for poor prognosis [3]. In gastric cancer, FNDC1 over-expression promotes tumorigenesis and metastasis, while knockdown inhibits them. Arsenite can suppress FNDC1 expression, attenuating the formation of a trimer complex related to cancer progression [4]. In breast cancer, FNDC1 promotes cell proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) through modulating the Wnt/β-catenin signaling pathway [5].

In conclusion, Fndc1 has essential functions in myogenesis and muscle regeneration, and is also involved in the progression of various cancers such as colorectal, lung, gastric, and breast cancers. The study of Fndc1 using gene knockout or other loss-of-function models helps to understand its role in these biological processes and disease conditions, providing potential targets for treating muscle diseases and cancers.