METTL13, also known as eEF1A-KNMT and FEAT, is a dual methyltransferase. It targets the N-terminus and Lys55 in eukaryotic translation elongation factor 1 alpha (eEF1A), and its methylation of eEF1A impacts translation dynamics, including global protein synthesis rates and translation of specific codons [4]. Aberrant regulation of METTL13 has been associated with multiple types of cancer, highlighting its importance in disease-related biological processes. Genetic models, such as gene knockout (KO) mouse models, can be valuable for studying METTL13's functions.

In Ras-driven cancers, METTL13-catalyzed eEF1A methylation increases eEF1A's GTPase activity and protein production, promoting tumorigenesis. METTL13 deletion and eEF1AK55me2 loss reduce Ras-driven neoplastic growth in mouse models and patient-derived xenografts from pancreatic and lung tumors [1]. In nasopharyngeal carcinoma (NPC), METTL13 silencing suppresses cellular phenotypes like proliferation, migration, invasion, and angiogenesis in vitro and hinders tumorigenesis in vivo [2]. In gastric cancer, silencing METTL13 suppresses cell proliferation and metastasis in vivo and vitro [3]. In clear cell renal cell carcinoma (ccRCC), knockdown of METTL13 in vitro leads to increased cell proliferation, viability, migratory and invasive abilities, while overexpression has the opposite effect. In vivo, METTL13 inhibits ccRCC cell growth and metastasis [5]. In bladder carcinoma, METTL13 was initially reported to negatively regulate cell proliferation, migration, and invasion, though the relevant paper was retracted later [6,7].

In conclusion, METTL13 plays a crucial role in tumor-related biological processes, as revealed through KO mouse models and other functional studies. Its role in promoting tumorigenesis in various cancers like Ras-driven, NPC, and gastric cancers, and its inhibitory effect on ccRCC progression, indicates its potential as a therapeutic target in cancer treatment.

References:

1. Liu, Shuo, Hausmann, Simone, Carlson, Scott Moore, Mazur, Pawel Karol, Gozani, Or. 2019. METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis. In Cell, 176, 491-504.e21. doi:10.1016/j.cell.2018.11.038. https://pubmed.ncbi.nlm.nih.gov/30612740/

2. Ni, Haifeng, Liang, Chengxian, Zhou, Zhen, Shang, Haiqiong, Yu, Xiaoyu. 2023. METTL13 promotes nasopharyngeal carcinoma progression through regulating the ZEB1/TPT1 axis. In The journal of gene medicine, 25, e3476. doi:10.1002/jgm.3476. https://pubmed.ncbi.nlm.nih.gov/36735630/

3. Wu, Qiong, Hu, Qingqing, Hai, Yanan, Li, Yandong, Gao, Yong. 2022. METTL13 facilitates cell growth and metastasis in gastric cancer via an eEF1A/HN1L positive feedback circuit. In Journal of cell communication and signaling, 17, 121-135. doi:10.1007/s12079-022-00687-x. https://pubmed.ncbi.nlm.nih.gov/35925508/

4. Jakobsson, Magnus E. 2021. Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13. In Life (Basel, Switzerland), 11, . doi:10.3390/life11111121. https://pubmed.ncbi.nlm.nih.gov/34832997/

5. Liu, Zhuonan, Sun, Tianshui, Piao, Chiyuan, Zhang, Zhe, Kong, Chuize. 2021. METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1α pathway and c-Myc expression. In Journal of translational medicine, 19, 209. doi:10.1186/s12967-021-02879-2. https://pubmed.ncbi.nlm.nih.gov/33985542/

6. Zhang, Zhe, Zhang, Guojun, Kong, Chuize, Dong, Xiao, Man, Xiaojun. 2016. METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion. In Scientific reports, 6, 19261. doi:10.1038/srep19261. https://pubmed.ncbi.nlm.nih.gov/26763933/

7. Zhang, Zhe, Zhang, Guojun, Kong, Chuize, Dong, Xiao, Man, Xiaojun. 2023. Retraction Note: METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion. In Scientific reports, 13, 11916. doi:10.1038/s41598-023-39010-y. https://pubmed.ncbi.nlm.nih.gov/37488192/