MTFR2, short for Mitochondrial fission regulator 2, belongs to the MTFR1 family and is crucial for regulating mitochondrial fission. It is also involved in metabolic reprogramming, particularly the shift from oxidative phosphorylation to glycolysis. MTFR2-related pathways include the Akt signaling pathway, and it is associated with important biological processes such as cancer-immunity cycle [2,3,4,7].

In hepatocellular carcinoma (HCC), MTFR2-dependent mitochondrial fission promotes HCC progression. Patients with heightened mitochondrial fission due to up-regulated MTFR2 have a worse prognosis. Down-regulation of MTFR2 in HCC cells blocks malignant behaviors, epithelial-to-mesenchymal transition (EMT), and glycolysis [1,3]. In oral squamous carcinoma, MTFR2 promotes cell proliferation, migration, and invasion by switching OXPHOS to glycolysis [4]. In lung adenocarcinoma, knockdown of MTFR2 inhibits cell proliferation, migration, and invasion via AKT-cyclin D1 signaling and EMT pathways [5]. In gastric cancer, down-regulation of MTFR2 inhibits the proliferation, migration, and invasion of GC cells in vitro and in vivo [6]. In breast cancer, knockdown of MTFR2 reduces the capacity for migration and invasion, and MTFR2 can switch glucose metabolism from OXPHS to glycolysis in a HIF1α-and HIF2α-dependent manner [7]. In endometrial carcinoma, MTFR2 promotes cell proliferation and growth through the miR-132-3p/PI3K/Akt signaling pathway [8].

In conclusion, MTFR2 plays a significant role in promoting the progression of multiple cancers, mainly through regulating mitochondrial fission and metabolic reprogramming. Loss-of-function experiments in various cancer cell lines have revealed its importance in processes like cell proliferation, migration, invasion, and metabolic shifts. Understanding MTFR2 provides potential targets for cancer therapy.

References:

1. Zhang, La, Zhang, Xiuzhen, Liu, Haichuan, Zhou, Baoyong, Jiang, Ning. 2024. MTFR2-dependent mitochondrial fission promotes HCC progression. In Journal of translational medicine, 22, 73. doi:10.1186/s12967-023-04845-6. https://pubmed.ncbi.nlm.nih.gov/38238834/

2. Huang, Qiaoqiao, Han, Ying, Shen, Edward, Cai, Changjing, Shen, Hong. 2022. MTFR2 shapes a barrier of immune microenvironment in hepatocellular carcinoma. In iScience, 26, 105095. doi:10.1016/j.isci.2022.105095. https://pubmed.ncbi.nlm.nih.gov/36713263/

3. Bao, Zhongming, Yang, Ming, Guo, Yunhu, Ge, Qi, Zhang, Huaguo. 2024. MTFR2 accelerates hepatocellular carcinoma mediated by metabolic reprogramming via the Akt signaling pathway. In Cellular signalling, 123, 111366. doi:10.1016/j.cellsig.2024.111366. https://pubmed.ncbi.nlm.nih.gov/39182591/

4. Wang, Wei, Xiong, Meihua, Jiang, Lin, Chen, Zean, Shao, Yisen. 2020. MTFR2 Promotes the Proliferation, Migration, and Invasion of Oral Squamous Carcinoma by Switching OXPHOS to Glycolysis. In Frontiers in oncology, 10, 858. doi:10.3389/fonc.2020.00858. https://pubmed.ncbi.nlm.nih.gov/32537437/

5. Lian, Zengzhi, Pang, Pei, Zhu, Yan, Du, Wenwen, Zhou, Jintao. 2022. Prognostic Value and Potential Mechanism of MTFR2 in Lung Adenocarcinoma. In Frontiers in oncology, 12, 832517. doi:10.3389/fonc.2022.832517. https://pubmed.ncbi.nlm.nih.gov/35600359/

6. Zhu, Hai, Wang, Gang, Zhu, Haixing, Xu, Aman. 2021. MTFR2, A Potential Biomarker for Prognosis and Immune Infiltrates, Promotes Progression of Gastric Cancer Based on Bioinformatics Analysis and Experiments. In Journal of Cancer, 12, 3611-3625. doi:10.7150/jca.58158. https://pubmed.ncbi.nlm.nih.gov/33995638/

7. Lu, Guanming, Lai, Yuanhui, Wang, Tiantian, Liu, Ruilei, Li, Jie. 2019. Mitochondrial fission regulator 2 (MTFR2) promotes growth, migration, invasion and tumour progression in breast cancer cells. In Aging, 11, 10203-10219. doi:10.18632/aging.102442. https://pubmed.ncbi.nlm.nih.gov/31740625/

8. Niu, Zhijun, Zhang, Yue, Wang, Yishan, Xu, Xia, Li, Lei. 2025. MTFR2 promotes endometrial carcinoma cell proliferation and growth via the miR-132-3p/PI3K/Akt signaling pathway. In Frontiers in medicine, 11, 1505071. doi:10.3389/fmed.2024.1505071. https://pubmed.ncbi.nlm.nih.gov/40129972/