MAGEC2,全称为Melanoma-associated antigen C2,是一种癌症/睾丸抗原,主要在睾丸和胎盘组织中表达,但在多种恶性肿瘤中高表达。它属于MAGE-I蛋白家族,这个家族的成员在正常组织中通常不表达,因此被视为癌症治疗的潜在靶点。MAGEC2的功能包括调节细胞生长、迁移和存活,以及与转录因子的相互作用,影响基因表达。
多篇研究表明,MAGEC2在多种癌症中扮演重要角色。例如,Beasley等人发现MAGEC2在乳腺癌细胞中表达受到高钙离子浓度的诱导,且其表达与肿瘤细胞的生长和迁移有关[1]。此外,MAGEC2的表达受到MAPK通路的调控,在H-RasV12或B-RafV600E突变的细胞中,MAGEC2的表达增加,并抑制了p53的转录活性,从而促进了肿瘤的发生[2]。Zeng等人发现MAGEC2与转录共激活因子TAF9相互作用,这可能揭示了MAGEC2在肿瘤细胞中的新的致癌功能[3]。在悬浮培养的肿瘤细胞中,MAGEC2的表达增加可以赋予细胞抵抗凋亡的能力,这可能与其维持STAT3的活性有关[4]。在肝细胞癌中,MAGEC2的表达与不良预后相关,其通过促进上皮-间质转化(EMT)来促进肿瘤的发生[5]。此外,MAGEC2还可以通过增强STAT3信号通路来促进肿瘤细胞的阿米巴样侵袭和转移[6]。
综上所述,MAGEC2在多种癌症中扮演重要角色,其表达受到多种信号通路的调控,包括MAPK通路和STAT3通路。MAGEC2的功能包括调节细胞生长、迁移和存活,以及与转录因子的相互作用,影响基因表达。这些发现为理解MAGEC2在肿瘤发生和发展中的作用提供了新的视角,并为癌症的治疗提供了潜在靶点。
参考文献:
1. Beasley, Heather K, Widatalla, Sarrah E, Whalen, Diva S, Ochieng, Josiah, Sakwe, Amos M. 2022. Identification of MAGEC2/CT10 as a High Calcium-Inducible Gene in Triple-Negative Breast Cancer. In Frontiers in endocrinology, 13, 816598. doi:10.3389/fendo.2022.816598. https://pubmed.ncbi.nlm.nih.gov/35355564/
2. Wang, Jingjing, Song, Xiao, Guo, Chengli, Wang, Ying, Yin, Yanhui. 2016. Establishment of MAGEC2-knockout cells and functional investigation of MAGEC2 in tumor cells. In Cancer science, 107, 1888-1897. doi:10.1111/cas.13082. https://pubmed.ncbi.nlm.nih.gov/27636589/
3. Pascucci, Franco Andrés, Ladelfa, María Fátima, Toledo, María Fernanda, Suberbordes, Melisa, Monte, Martín. 2020. MageC2 protein is upregulated by oncogenic activation of MAPK pathway and causes impairment of the p53 transactivation function. In Biochimica et biophysica acta. Molecular cell research, 1868, 118918. doi:10.1016/j.bbamcr.2020.118918. https://pubmed.ncbi.nlm.nih.gov/33279609/
4. Zeng, Pumei, Wang, Ying, Zheng, Yutian, Song, Xiao, Yin, Yanhui. 2017. Cancer‑testis antigen HCA587/MAGEC2 interacts with the general transcription coactivator TAF9 in cancer cells. In Molecular medicine reports, 17, 3226-3231. doi:10.3892/mmr.2017.8260. https://pubmed.ncbi.nlm.nih.gov/29257297/
5. Park, Doyeon, Han, Sora, Joo, Hyunjeong, Park, Jiyoung, Yang, Young. 2021. Increased Melanoma-Associated Antigen C2 Expression Affords Resistance to Apoptotic Deathin Suspension-Cultured Tumor Cells. In Journal of breast cancer, 24, 138-152. doi:10.4048/jbc.2021.24.e6. https://pubmed.ncbi.nlm.nih.gov/33818016/
6. Gu, Xuefeng, Mao, Yuan, Shi, Chuanbing, Chen, Yan, Zhao, Wei. 2019. MAGEC2 Correlates With Unfavorable Prognosis And Promotes Tumor Development In HCC Via Epithelial-Mesenchymal Transition. In OncoTargets and therapy, 12, 7843-7855. doi:10.2147/OTT.S213164. https://pubmed.ncbi.nlm.nih.gov/31576142/