Pcmt1-KO Mouse

PCMT1, also known as protein-L-isoaspartate (D-aspartate) O-methyltransferase, is a repair enzyme. It catalyzes the conversion of isomerized aspartic acid (iso-Asp) residues into their normal structure, restoring the configuration and function of proteins [2]. It has been implicated in various pathways related to cancer progression, such as the integrin-FAK-Src pathway [1], and the PI3K/AKT/GSK-3β pathway [2].

Genome-wide CRISPR/Cas9 knockout screen identified PCMT1 as a critical driver of anoikis resistance in ovarian cancer. PCMT1 knockdown/knockout experiments showed that it enhanced cell migration, adhesion, and spheroid formation in vitro, and in vivo, overexpression led to increased ascites formation and distant metastasis, while knockout had the opposite effect [1]. In prostate cancer, PCMT1 knockdown/overexpression experiments demonstrated that it promoted cell proliferation, migration, invasion, and inhibited apoptosis, acting through the PI3K/AKT/GSK-3β pathway [2]. In liver cancer, in vitro and in vivo experiments with PCMT1 knockdown showed inhibition of cancer cell proliferation and migration, promotion of apoptosis, and reduced tumor growth rate [3]. In breast cancer, in vitro experiments with PCMT1 knockdown decreased cell migration and invasiveness, and animal studies confirmed that its inhibition slowed tumor growth [4]. Also, silencing PCMT1 enhanced the sensitivity of breast cancer cells to paclitaxel [5]. In cervical cancer, high expression of PCMT1 was associated with decreased overall survival [6]. In bladder cancer, PCMT1 regulated cell migration and invasion through modulating epithelial-mesenchymal transition (EMT)-associated genes, and its high-expression was an independent unfavorable prognostic factor [7].

In conclusion, PCMT1 plays a significant role in cancer-related biological processes. Through gene knockout and knockdown studies in various cancer models, it has been shown to promote cancer cell proliferation, migration, invasion, and inhibit apoptosis, and is related to poor prognosis in multiple cancers. These findings highlight the potential of PCMT1 as a therapeutic target in cancer treatment.

References:

1. Zhang, Jingjing, Li, Yun, Liu, Hua, Xu, Yingjie, Feng, Weiwei. 2022. Genome-wide CRISPR/Cas9 library screen identifies PCMT1 as a critical driver of ovarian cancer metastasis. In Journal of experimental & clinical cancer research : CR, 41, 24. doi:10.1186/s13046-022-02242-3. https://pubmed.ncbi.nlm.nih.gov/35033172/

2. Zhong, Jiacheng, Yuan, Chao, Liu, Lin, Liu, Guiyong, Liu, Xiuheng. 2023. PCMT1 regulates the migration, invasion, and apoptosis of prostate cancer through modulating the PI3K/AKT/GSK-3β pathway. In Aging, 15, 11654-11671. doi:10.18632/aging.205152. https://pubmed.ncbi.nlm.nih.gov/37899170/

3. Liu, Jiahao, Liu, Baiying, Li, Yanan, Tan, Hongpei, Rong, Pengfei. 2023. PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer. In European journal of medical research, 28, 289. doi:10.1186/s40001-023-01216-1. https://pubmed.ncbi.nlm.nih.gov/37596654/

4. Liu, Yiqi, Li, Haobing, Shen, Xiangyu, Zhong, Jing, Cao, Renxian. 2024. PCMT1 confirmed as a pan-cancer immune biomarker and a contributor to breast cancer metastasis. In American journal of cancer research, 14, 3711-3732. doi:10.62347/TYLL7952. https://pubmed.ncbi.nlm.nih.gov/39267673/

5. Zhang, Ke, Li, Jin-You, Li, Kai. . Silencing PCMT1 enhances the sensitivity of breast cancer cells to paclitaxel through the PI3K/Akt/STMN1 pathway. In Chemical biology & drug design, 103, e14559. doi:10.1111/cbdd.14559. https://pubmed.ncbi.nlm.nih.gov/38853025/

6. Shan, Liyun, Wang, Xiaoyun, Li, Yanli, Xi, Xiaowei, Yang, Yongbin. . Elevated expression of protein-L-isoaspartate O-methyltransferase-1 (PCMT1) in cervical cancer. In Translational cancer research, 11, 2582-2590. doi:10.21037/tcr-21-2700. https://pubmed.ncbi.nlm.nih.gov/36093534/

7. Dong, Liming, Li, Yanpei, Xue, Dongwei, Liu, Yili. 2018. PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer. In IUBMB life, 70, 291-299. doi:10.1002/iub.1717. https://pubmed.ncbi.nlm.nih.gov/29517839/