基因Sdcbp,也称为Syndecan Binding Protein(Syntenin)或Melanoma Differentiation Associated Gene-9(MDA-9),编码一种PDZ结构域含有的蛋白质,参与细胞粘附、迁移和信号转导等细胞过程。Sdcbp在多种癌症中表达上调,尤其是在转移性癌细胞中,因此被认为是治疗癌症转移的潜在靶点。
研究表明,Sdcbp在多种癌症的进展和转移中发挥重要作用。例如,在一项针对胰腺导管腺癌(PDAC)的研究中,发现Sdcbp通过阻止YAP1蛋白的β-TrCP介导的泛素化降解,促进PDAC的增殖和转移[2]。此外,在结直肠癌中,高表达Sdcbp与对免疫治疗的非反应性和较差的无病生存率相关。抑制Sdcbp可以抑制结直肠癌的增殖和转移,并增强免疫治疗的疗效[4]。Sdcbp还在黑色素瘤、肝细胞癌等多种癌症的进展和转移中发挥重要作用[1,6]。
除了在癌症中的作用,Sdcbp还与其他疾病相关。例如,研究发现,Sdcbp在急性心肌梗死(AMI)后心力衰竭(HF)的发生中发挥重要作用。Sdcbp在AMI后表达上调,并与AMI后HF的发生风险增加相关[3]。
Sdcbp还与病毒感染有关。研究发现,非洲猪瘟病毒(ASFV)的MGF360-16R基因编码的蛋白与宿主蛋白SERTAD3和SDCBP相互作用[5]。这些发现表明,Sdcbp可能参与病毒感染和复制过程。
Sdcbp作为一种多功能支架蛋白,参与多种生物学过程,包括细胞粘附、迁移、信号转导、炎症反应和病毒感染等。Sdcbp在癌症、心血管疾病和病毒感染等多种疾病中发挥重要作用。因此,Sdcbp被认为是治疗这些疾病的潜在靶点。
参考文献:
1. Das, Swadesh K, Maji, Santanu, Wechman, Stephen L, Emdad, Luni, Fisher, Paul B. 2020. MDA-9/Syntenin (SDCBP): Novel gene and therapeutic target for cancer metastasis. In Pharmacological research, 155, 104695. doi:10.1016/j.phrs.2020.104695. https://pubmed.ncbi.nlm.nih.gov/32061839/
2. Liu, Jing, Bai, Weiwei, Zhou, Tianxing, Yang, Shengyu, Hao, Jihui. 2023. SDCBP promotes pancreatic cancer progression by preventing YAP1 from β-TrCP-mediated proteasomal degradation. In Gut, 72, 1722-1737. doi:10.1136/gutjnl-2022-327492. https://pubmed.ncbi.nlm.nih.gov/36828627/
3. Chen, Qixin, Su, Lina, Liu, Chuanfen, Yin, Qijin, Li, Sufang. 2022. PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction. In Frontiers in immunology, 13, 878876. doi:10.3389/fimmu.2022.878876. https://pubmed.ncbi.nlm.nih.gov/35592331/
4. Yu, Jiahua, Yu, Shijun, Bai, Jin, Gao, Yong, Li, Yandong. 2024. SDCBP modulates tumor microenvironment, tumor progression and anti-PD1 efficacy in colorectal cancer. In Cancer gene therapy, 31, 755-765. doi:10.1038/s41417-024-00758-8. https://pubmed.ncbi.nlm.nih.gov/38555398/
5. Ramírez-Medina, Elizabeth, Vuono, Elizabeth A, Velazquez-Salinas, Lauro, Borca, Manuel V, Gladue, Douglas P. 2020. The MGF360-16R ORF of African Swine Fever Virus Strain Georgia Encodes for a Nonessential Gene That Interacts with Host Proteins SERTAD3 and SDCBP. In Viruses, 12, . doi:10.3390/v12010060. https://pubmed.ncbi.nlm.nih.gov/31947814/
6. Manna, Debashri, Reghupaty, Saranya Chidambaranathan, Camarena, Maria Del Carmen, Fisher, Paul B, Sarkar, Devanand. 2023. Melanoma differentiation associated gene-9/syndecan binding protein promotes hepatocellular carcinoma. In Hepatology (Baltimore, Md.), 78, 1727-1741. doi:10.1002/hep.32797. https://pubmed.ncbi.nlm.nih.gov/36120720/