Fndc1, or fibronectin type III domain containing 1, is a gene with significant biological importance. It has been implicated in various biological processes and associated with multiple signaling pathways. In myogenesis, it promotes myogenic differentiation through binding to integrin α5β1 and activating the FAK/PI3K/AKT/mTOR pathway [1]. In cancer, it is involved in processes such as cell survival, stemness, and metastasis, often associated with the PI3K/Akt, JAK-STAT, and Wnt/β -catenin signaling pathways [2,3,4,5,6,7].

Gain-and loss-of-function studies, including knockdown and overexpression in myoblasts, have shown that Fndc1 promotes myotube formation and cardiotoxin-induced muscle regeneration in adult mice [1]. In cancer research, knockdown of Fndc1 in various cancer cell lines, such as colorectal, gastric, and breast cancer cells, has demonstrated its role in inhibiting cell proliferation, migration, invasion, and metastasis [2,4,6,7]. For example, in gastric cancer, knockdown of Fndc1 suppresses tumorigenesis and metastasis by interfering with the formation of the TWIST1-Gβγ-VEGFR2 trimer and downstream pathways [4].

In conclusion, Fndc1 plays essential roles in myogenesis and muscle regeneration, and its dysregulation is associated with the progression of multiple cancers. Model-based research, especially knockdown and overexpression studies, has been crucial in revealing its functions in these biological processes and disease conditions. These findings provide potential therapeutic targets for muscle diseases and cancer treatment.

References:

1. Zhang, Rui Xin, Zhai, Yuan Yuan, Ding, Rong Rong, Xia, Bo, Wu, Jiang Wei. 2024. FNDC1 is a myokine that promotes myogenesis and muscle regeneration. In The EMBO journal, 44, 30-53. doi:10.1038/s44318-024-00285-0. https://pubmed.ncbi.nlm.nih.gov/39567831/

2. Chen, Lin, Liu, Jie, Wang, Lingfei, Zhou, Zhuqing, Fu, Chuangang. 2022. Up-regulated FNDC1 accelerates stemness and chemoradiation resistance in colorectal cancer cells. In Biochemical and biophysical research communications, 602, 84-90. doi:10.1016/j.bbrc.2022.02.038. https://pubmed.ncbi.nlm.nih.gov/35255438/

3. Hong, H, Zhu, H, Li, C, Chen, L, Wang, A. . [FNDC1 is highly expressed in lung adenocarcinoma and closely related with poor prognosis]. In Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 42, 1182-1190. doi:10.12122/j.issn.1673-4254.2022.08.10. https://pubmed.ncbi.nlm.nih.gov/36073217/

4. Lu, Yao, Huang, Panpan, Zeng, Xueliang, Liu, Xiaojian, Wei, Hulai. 2023. Inhibition of FNDC1 suppresses gastric cancer progression by interfering with Gβγ-VEGFR2 complex formation. In iScience, 26, 107534. doi:10.1016/j.isci.2023.107534. https://pubmed.ncbi.nlm.nih.gov/37670789/

5. Song, Yang, Guo, Jun-Feng, Lan, Pei-Shu, Wang, Miao, Du, Quan-Yu. 2024. Investigation of the pan-cancer property of FNDC1 and its molecular mechanism to promote lung adenocarcinoma metastasis. In Translational oncology, 44, 101953. doi:10.1016/j.tranon.2024.101953. https://pubmed.ncbi.nlm.nih.gov/38593585/

6. Jiang, Tao, Gao, Wenyu, Lin, Shengjie, Lin, Xiaoyan, Chen, Qiang. 2020. FNDC1 Promotes the Invasiveness of Gastric Cancer via Wnt/β-Catenin Signaling Pathway and Correlates With Peritoneal Metastasis and Prognosis. In Frontiers in oncology, 10, 590492. doi:10.3389/fonc.2020.590492. https://pubmed.ncbi.nlm.nih.gov/33392086/

7. Fan, Guocai, Zhang, Chen. 2024. FNDC1 Facilitates Proliferation, Migration, and Invasion of Breast Cancer Cells Through Modulating Wnt/β-Catenin Pathway. In Biochemical genetics, , . doi:10.1007/s10528-024-10994-0. https://pubmed.ncbi.nlm.nih.gov/39671143/