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Updated: May 18, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Tumour promoting functions of TGF-β in CML-initiating cells
1Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan. miyazono@m.u-tokyo.ac.jp
Abstract:
Recent data have shown that transforming growth factor-β (TGF-β) plays bi-directional roles in the maintenance of cancer stem cells in a cell-type and context-dependent manner. Zhu et al. (TGF-β1-induced PI3K/Akt/NF-κB/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts. J. Biochem. 2011;149:405-414) studied the functions of TGF-β in hemangioblasts from patients with chronic myeloid leukemia (CML), which displayed properties of leukemia-initiating cells. They have shown that the BCR/ABL oncoprotein induced the production of TGF-β in the CML hemangioblasts, and that TGF-β activated the phosphoinositide 3-kinase-Akt-NF-κB pathway in these cells. Activation of this pathway enhanced the production of matrix metalloproteinase-9 leading to increased synthesis of soluble Kit ligand and intercellular adhesion molecule-1. TGF-β is known to maintain the CML-initiating cells through the Akt-FoxO pathway. Together, these findings suggest that TGF-β may exhibit multiple functions in progression of CML through acting on leukemia-initiating cells.
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