Spock1,也称为SPARC(骨连接蛋白)/osteonectin,cwcv和kazal-like domains proteoglycan 1,是一种高度保守的多结构域蛋白聚糖。它主要在细胞外基质(ECM)中发挥调节作用,参与ECM的动态平衡。Spock1的表达在不同类型的癌症中存在差异,且与癌症的进展和预后密切相关。在多种癌症中,Spock1的表达升高与肿瘤细胞的增殖、侵袭和转移能力增强有关。此外,Spock1还参与了多种信号通路的调控,包括上皮-间质转化(EMT)过程、Wnt/β-catenin信号通路、PI3K/Akt信号通路和mTOR/S6K信号通路。Spock1的异常表达还与肿瘤微环境重塑、药物敏感性以及免疫细胞浸润相关。
Spock1在多种癌症中发挥重要作用。在肺腺癌中,Spock1的表达升高与不良预后相关。Spock1通过促进EMT和免疫逃逸在肺腺癌的进展中发挥重要作用。此外,Spock1的表达升高还与肿瘤微环境重塑和药物敏感性相关[1]。在结直肠癌中,Spock1的表达升高与对5-氟尿嘧啶(5-FU)的耐药性相关。Spock1通过调节PRRX1表达和下游的细胞凋亡信号通路,促进结直肠癌细胞对5-FU的耐药性[2]。在肺癌中,Spock1的表达升高与肿瘤的转移和不良预后相关。Spock1通过激活TGF-β信号通路,促进肺癌细胞的EMT和转移[3]。在胰腺癌中,Spock1的表达升高与肿瘤的侵袭和转移能力增强相关。Spock1通过激活NF-κB信号通路,促进胰腺癌细胞的EMT和转移[5]。在肾细胞癌中,Spock1的表达升高与肿瘤的侵袭和转移能力增强相关。Spock1通过激活Snail/Slug-MMP-2轴,促进肾细胞癌的EMT和转移[4]。
Spock1的研究有助于深入理解其在肿瘤发生发展中的作用机制,为癌症的治疗和预防提供新的思路和策略。针对Spock1的靶向治疗可能成为多种癌症治疗的新策略。
参考文献:
1. Liu, Yafeng, Han, Tao, Wu, Jing, Bai, Ying, Hu, Dong. 2023. SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion. In Journal of translational medicine, 21, 909. doi:10.1186/s12967-023-04616-3. https://pubmed.ncbi.nlm.nih.gov/38087364/
2. Qu, Yu-Ling, Liu, Xiao-Li, Zhao, Shan-Yu, Zhai, Xue-Feng. 2022. SPOCK1 silencing decreases 5-FU resistance through PRRX1 in colorectal cancer. In Pathology, research and practice, 234, 153895. doi:10.1016/j.prp.2022.153895. https://pubmed.ncbi.nlm.nih.gov/35462225/
3. Miao, Liyun, Wang, Yongsheng, Xia, Hongping, Cai, Hourong, Song, Yong. 2013. SPOCK1 is a novel transforming growth factor-β target gene that regulates lung cancer cell epithelial-mesenchymal transition. In Biochemical and biophysical research communications, 440, 792-7. doi:10.1016/j.bbrc.2013.10.024. https://pubmed.ncbi.nlm.nih.gov/24134845/
4. Lin, Yung-Wei, Wen, Yu-Ching, Hsiao, Chi-Hao, Lee, Wei-Jiunn, Chien, Ming-Hsien. 2023. Proteoglycan SPOCK1 as a Poor Prognostic Marker Promotes Malignant Progression of Clear Cell Renal Cell Carcinoma via Triggering the Snail/Slug-MMP-2 Axis-Mediated Epithelial-to-Mesenchymal Transition. In Cells, 12, . doi:10.3390/cells12030352. https://pubmed.ncbi.nlm.nih.gov/36766694/
5. Cui, Xuelian, Wang, Yixuan, Lan, Weiqiang, Lin, Zhenhua, Piao, Junjie. 2021. SPOCK1 promotes metastasis in pancreatic cancer via NF-κB-dependent epithelial-mesenchymal transition by interacting with IκB-α. In Cellular oncology (Dordrecht, Netherlands), 45, 69-84. doi:10.1007/s13402-021-00652-7. https://pubmed.ncbi.nlm.nih.gov/34855159/