Tagln, also known as transgelin or SM22, is an actin-associated protein that affects the dynamics of actin filaments. It can cross-link and gel actin, and is involved in multiple cellular processes. TAGLN is associated with pathways like RhoA/ROCK, NF-κB, and Myc signaling, and plays a significant role in various biological processes and disease conditions [1,2]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its function.

In ovarian cancer, TAGLN forms a regulation loop with Src activation in response to environmental stiffness, mediating cancer progression through the RhoA/ROCK pathway, suggesting targeting it could have therapeutic value [1]. In prostate cancer, E3 ligase TRAF6 mediates the mono-ubiquitination and degradation of TAGLN, leading to the activation of NF-κB and Myc signaling pathways. Ablation of TAGLN promotes cell proliferation and suppresses migration [2]. In skin fibrosis, downregulation of TAGLN inhibits fibroblast motility and secretory function, and TAGLN regulates the glucose carrier SLC2A3 through the RhoA/ROCK2 pathway [3]. In colorectal cancer, inhibition of TAGLN reverses TGF-β-induced cell migration and invasion, and the interaction between TAGLN and HMGA2 is involved in TGF-β-induced cell migration and cancer cell promotion [4]. Also, in colorectal carcinoma cells, TAGLN suppresses proliferation and invasion, and induces apoptosis [5].

In conclusion, TAGLN is crucial in regulating cellular processes related to cancer progression, fibrosis, and cell-matrix interactions. Studies using KO/CKO mouse models have revealed its role in ovarian, prostate, colorectal cancers, and skin fibrosis. Understanding TAGLN's functions provides potential therapeutic targets for these diseases.

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. 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/

4. 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/

5. 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/