Tagln,也称为Transgelin或SM22,是一种与肌动蛋白相关的蛋白质,主要表达于血管平滑肌细胞和某些肿瘤细胞中。Tagln在细胞内通过与其他蛋白质相互作用,如肌动蛋白和钙调蛋白,参与调节细胞骨架的动态变化,进而影响细胞的增殖、迁移、侵袭和凋亡等生物学行为。此外,Tagln还与细胞外基质(ECM)的稳定性和组织硬度有关,可能在肿瘤的发生、发展和转移中发挥重要作用。
Tagln在多种疾病中发挥重要作用。在卵巢癌中,Tagln作为一种机械敏感基因,能够响应环境硬度的变化,通过调节RhoA/ROCK信号通路,进而影响卵巢癌的进展[1]。在动脉粥样硬化中,Tagln的表达降低与不稳定的动脉粥样硬化斑块形成相关,表明Tagln可能在维持斑块稳定性方面发挥重要作用[2]。此外,Tagln在结直肠癌、前列腺癌和非小细胞肺癌等肿瘤中表达降低,表明Tagln可能作为一种肿瘤抑制因子,通过抑制肿瘤细胞的增殖、迁移和侵袭,以及促进肿瘤细胞的凋亡,从而发挥抑癌作用[3,5,6]。
Tagln的表达和功能受到多种因素的调控。在前列腺癌中,Tagln的表达下调是由于TRAF6介导的泛素化降解所致,TRAF6通过催化Tagln的泛素化,促进其被蛋白酶体降解,进而导致NF-κB和Myc信号通路的激活,促进肿瘤细胞的增殖[4]。此外,Tagln的表达还受到其他信号通路的调控,如LZTS3通过靶向NOTCH信号通路,抑制结直肠腺癌细胞的增殖和迁移[7]。
Tagln的研究为肿瘤和动脉粥样硬化等疾病的治疗提供了新的思路和策略。针对Tagln的靶向治疗,如恢复Tagln的表达或抑制Tagln的降解,可能成为治疗肿瘤和动脉粥样硬化等疾病的有效方法。此外,Tagln的表达水平和功能状态可能作为疾病诊断和预后的生物标志物,为疾病的早期发现和治疗提供重要参考。
参考文献:
1. Wei, Xiao, Lou, Hua, Zhou, Dongchen, Guo, Zhongzhen, Gao, Qinglei. 2021. TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway. In Journal of experimental & clinical cancer research : CR, 40, 292. doi:10.1186/s13046-021-02091-6. https://pubmed.ncbi.nlm.nih.gov/34538264/
2. Wang, Jing, Kang, Zijian, Liu, Yandong, Liu, Yang, Liu, Jianmin. 2022. Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learning. In Frontiers in immunology, 13, 956078. doi:10.3389/fimmu.2022.956078. https://pubmed.ncbi.nlm.nih.gov/36211422/
3. Zhou, Yuan, Bian, Shuhui, Zhou, Xin, Fu, Wei, Tang, Fuchou. 2020. Single-Cell Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer. In Cancer cell, 38, 818-828.e5. doi:10.1016/j.ccell.2020.09.015. https://pubmed.ncbi.nlm.nih.gov/33096021/
4. Woo, Sang-Ho, Kyung, Dongsoo, Lee, Seung Hyun, Choi, Jae-Hoon, Kim, Dae-Yong. 2022. TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis. In Circulation research, 132, 52-71. doi:10.1161/CIRCRESAHA.122.321538. https://pubmed.ncbi.nlm.nih.gov/36448450/
5. Wen, Fuping, Sun, Xiaochen, Sun, Chenxia, Yu, Haolan, Yang, Chenghua. 2021. TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells. In Molecular cancer research : MCR, 19, 1113-1122. doi:10.1158/1541-7786.MCR-20-0513. https://pubmed.ncbi.nlm.nih.gov/33771884/
6. Li, Qinmin, Shi, Ruihua, Wang, Yundong, Niu, Xiaoping. 2012. TAGLN suppresses proliferation and invasion, and induces apoptosis of colorectal carcinoma cells. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 34, 505-13. doi:10.1007/s13277-012-0575-0. https://pubmed.ncbi.nlm.nih.gov/23138394/
7. Gu, Xinpei, Chen, Shuhui, Wang, Zhaojin, Bu, Qianwen, An, Shuhong. 2023. LZTS3/TAGLN Suppresses Cancer Progression in Human Colorectal Adenocarcinoma Through Regulating Cell Proliferation, Migration, and Actin Cytoskeleton. In Archives of medical research, 54, 102894. doi:10.1016/j.arcmed.2023.102894. https://pubmed.ncbi.nlm.nih.gov/37806182/