Jia Ding, Yong-Yu Yang, Peng-Tao Li, Yue Ma, Li Zhang, Yuan Zhou, Cheng Jin, Hui-Yan Li, Yuan-Fei Zhu, Xiu-Ping Liu, Zheng-Jin Liu, Hu-Liang Jia, Ping-Guo Liu, Jian Wu
Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-β1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-β1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells...
March 5, 2024: Cancer Letters