title: Tumour promoting functions of TGF-β in CML-initiating cells.
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.
authors.affiliation: Department 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
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
mesh_terms: D005260:Female; D055018:Hemangioblasts / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D058539:Phosphatidylinositol 3-Kinase; D020780:Matrix Metalloproteinase 9