Srcin1(Src激酶信号抑制剂1)是一种编码适配蛋白p140Cap的基因,p140Cap是p130Cas/BCAR1的关联蛋白。p130Cas/BCAR1是一种缺乏任何酶促或转录活性的适配蛋白,其模块结构具有多种结合基序,可以形成多蛋白信号复合物,从而诱导和/或维持对细胞运动、细胞粘附、细胞骨架重塑、侵袭、生存和增殖有广泛影响的信号通路。p140Cap通过与Src激酶的相互作用与p130Cas关联,而非直接与p130Cas结合。p140Cap在神经元中高度表达,在乳腺等上皮组织中表达较少。在乳腺癌和神经母细胞瘤中,肿瘤组织中p140Cap的表达与肿瘤进展呈负相关,表明其具有肿瘤抑制功能[2]。
Srcin1在多种癌症中发挥着不同的作用。在乳腺癌中,Srcin1的过度甲基化被发现与乳腺癌细胞增殖有关,并且是一种潜在的基于血液的生物标志物,可以用于早期检测和不良预后的评估[1]。此外,Srcin1的过度表达与非小细胞肺癌(NSCLC)肿瘤生长和上皮-间质转化(EMT)诱导有关[4]。然而,在结直肠癌(CRC)中,Srcin1的表达增加与肿瘤进展相关,Srcin1的抑制可以诱导细胞分化、G0/G1细胞周期阻滞,并增加CRC细胞对5-氟尿嘧啶(5-FU)诱导的细胞凋亡的敏感性[3]。此外,Srcin1在骨肉瘤细胞中下调,Srcin1的过表达可以抑制骨肉瘤细胞MG-63的增殖,并抑制其侵袭和转移[5]。
Srcin1的表达和功能受多种microRNA(miRNA)的调控。例如,miR-657和miR-150-5p可以下调Srcin1的表达,并促进NSCLC和乳腺癌的增殖、侵袭和迁移[4,6]。相反,miR-346和miR-665可以抑制Srcin1的表达,并促进皮肤鳞状细胞癌和卵巢癌细胞的增殖和迁移[7,8]。
综上所述,Srcin1在多种癌症中发挥着复杂的作用,其表达和功能受多种miRNA的调控。Srcin1的研究有助于深入理解癌症发生和发展的机制,为癌症的诊断和治疗提供新的思路和策略。
参考文献:
1. Shen, Hsieh-Tsung, Hung, Chin-Sheng, Davis, Clilia, Ansar, Muhamad, Lin, Ruo-Kai. 2024. Hypermethylation of the Gene Body in SRCIN1 Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis. In Biomolecules, 14, . doi:10.3390/biom14050571. https://pubmed.ncbi.nlm.nih.gov/38785978/
2. Centonze, Giorgia, Natalini, Dora, Salemme, Vincenzo, Cabodi, Sara, Defilippi, Paola. 2021. p130Cas/BCAR1 and p140Cap/SRCIN1 Adaptors: The Yin Yang in Breast Cancer? In Frontiers in cell and developmental biology, 9, 729093. doi:10.3389/fcell.2021.729093. https://pubmed.ncbi.nlm.nih.gov/34708040/
3. Zhang, Mengnan, Ma, Feng, Xie, Ruyi, Wang, Jide, Chen, Xueqing. 2017. Overexpression of Srcin1 contributes to the growth and metastasis of colorectal cancer. In International journal of oncology, 50, 1555-1566. doi:10.3892/ijo.2017.3952. https://pubmed.ncbi.nlm.nih.gov/28393242/
4. Zhang, Yingqian, Yuan, Jiao, Guo, Mengfei, Li, Qiang, Lai, Qi. 2022. miR-657 Targets SRCIN1 via the Slug Pathway to Promote NSCLC Tumor Growth and EMT Induction. In Disease markers, 2022, 4842454. doi:10.1155/2022/4842454. https://pubmed.ncbi.nlm.nih.gov/36033827/
5. Wang, Peng, Wang, Hu, Li, Xiaotao, Zhao, Chengbin, Zhu, Daling. 2016. SRCIN1 Suppressed Osteosarcoma Cell Proliferation and Invasion. In PloS one, 11, e0155518. doi:10.1371/journal.pone.0155518. https://pubmed.ncbi.nlm.nih.gov/27513473/
6. Lu, Qingfu, Guo, Zhaoji, Qian, Haixin. 2019. Role of microRNA-150-5p/SRCIN1 axis in the progression of breast cancer. In Experimental and therapeutic medicine, 17, 2221-2229. doi:10.3892/etm.2019.7206. https://pubmed.ncbi.nlm.nih.gov/30867707/
7. Chen, Bin, Pan, Wenyan, Lin, Xiaoxi, Ying, Hanru, Lv, Dongze. 2015. MicroRNA-346 functions as an oncogene in cutaneous squamous cell carcinoma. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 2765-71. doi:10.1007/s13277-015-4046-2. https://pubmed.ncbi.nlm.nih.gov/26408183/
8. Zhou, Ping, Xiong, Tingchuan, Yao, Lili, Yuan, Jianlin. 2019. MicroRNA-665 promotes the proliferation of ovarian cancer cells by targeting SRCIN1. In Experimental and therapeutic medicine, 19, 1112-1120. doi:10.3892/etm.2019.8293. https://pubmed.ncbi.nlm.nih.gov/32010277/