Tagln, also named Transgelin or SM22, is an actin-associated protein that affects actin filament dynamics. It can cross-link/gel actin and is involved in multiple cellular processes. The RhoA/ROCK pathway is one of the associated pathways, and Tagln is important in mediating mechanotransduction, which bridges the mechanical environment of tissues and cellular metabolism [1,4].

In cancer research, in ovarian cancer, Tagln was identified as a mechanosensitive gene. Matrix stiffness could regulate ovarian cancer progression, and Tagln mediated this process through the RhoA/ROCK pathway [1]. In prostate cancer, Tagln is usually downregulated via TRAF6-mediated proteasomal degradation. Ablation of Tagln promoted cell proliferation and suppressed migration through activation of NF-κB and Myc signaling pathways [2]. In colorectal cancer, the interaction between Tagln and HMGA2 was involved in TGF-β-induced cell migration and promotion of cancer cells, and inhibition of Tagln reversed the effects of TGF-β on cell migration and invasion [5]. Also, Tagln suppresses the proliferation, invasion, and induces apoptosis of colorectal carcinoma cells, and inhibits the expression of MMP9 [7]. In glioblastoma, hypoxia preferentially induces Tagln in GBM stem cells, and Tagln regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal [8].

In non-cancer related research, in endometriosis, Fusobacterium infection led to the transition from quiescent fibroblasts to Tagln-positive myofibroblasts, promoting the development of endometriosis [3]. In skin fibrosis, the TAGLN-RhoA/ROCK2-SLC2A3 mechano-metabolic axis was found to promote skin fibrosis, and downregulation of Tagln inhibited fibroblast motility and secretory function [4]. In skin photoaging, UVA-induced upregulation of Tagln led to an imbalance between dermal matrix synthesis and degradation. Tagln interacted with USP1, promoted ZEB1 ubiquitination degradation, and caused photoaging [6].

In conclusion, Tagln is crucial in various biological processes and diseases. Its role in cancer, endometriosis, skin fibrosis, and photoaging has been revealed through different studies. Understanding Tagln function in these disease areas helps provide potential molecular targets for treatment and prevention.

References:

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. 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/

3. Muraoka, Ayako, Suzuki, Miho, Hamaguchi, Tomonari, Kajiyama, Hiroaki, Kondo, Yutaka. 2023. Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts. In Science translational medicine, 15, eadd1531. doi:10.1126/scitranslmed.add1531. https://pubmed.ncbi.nlm.nih.gov/37315109/

4. Cheng, Xinwei, Gao, Zhen, Zhang, Jin, Shan, Shengzhou, Zhou, Jia. 2025. TAGLN-RhoA/ROCK2-SLC2A3-mediated Mechano-metabolic Axis Promotes Skin Fibrosis. In International journal of biological sciences, 21, 658-670. doi:10.7150/ijbs.104484. https://pubmed.ncbi.nlm.nih.gov/39781462/

5. Zhou, Huimin, Li, Lan, Xie, Wenrui, Lin, Ying, He, Xingxiang. 2020. TAGLN and High-mobility Group AT-Hook 2 (HMGA2) Complex Regulates TGF-β-induced Colorectal Cancer Metastasis. In OncoTargets and therapy, 13, 10489-10498. doi:10.2147/OTT.S263090. https://pubmed.ncbi.nlm.nih.gov/33116628/

6. Li, Yinan, Huang, Xiu, Jin, Jing, Zhu, Caibin, Liu, Huijuan. 2023. Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging. In Cell & bioscience, 13, 80. doi:10.1186/s13578-023-01029-z. https://pubmed.ncbi.nlm.nih.gov/37149635/

7. 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/

8. Li, Huan, Song, Chao, Zhang, Yang, Rich, Jeremy N, Yu, Xingjiang. 2023. Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2305620. doi:10.1002/advs.202305620. https://pubmed.ncbi.nlm.nih.gov/38087889/