Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
J Biochem. 2012 Nov;152(5):383-5. doi: 10.1093/jb/mvs106. Epub 2012 Sep 17.
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.
最近的数据表明，转化生长因子-β（TGF-β）在以细胞类型和上下文依赖的方式维持癌症干细胞中发挥双向作用。Zhu 等人（TGF-β1 诱导的 PI3K/Akt/NF-κB/MMP9 信号通路在费城染色体阳性慢性髓性白血病血球母细胞中被激活。J. Biochem. 2011;149:405-414）研究了 TGF-β 在慢性髓性白血病（CML）患者血球母细胞中的功能，这些血球母细胞具有白血病起始细胞的特性。他们表明，BCR/ABL 癌蛋白诱导 CML 血球母细胞产生 TGF-β，而 TGF-β 激活了这些细胞中的磷酸肌醇 3-激酶-Akt-NF-κB 途径。该途径的激活增强了基质金属蛋白酶-9 的产生，导致可溶性 Kit 配体和细胞间黏附分子-1 的合成增加。已知 TGF-β 通过 Akt-FoxO 途径维持 CML 起始细胞。综上所述，这些发现表明 TGF-β 可能通过作用于白血病起始细胞在 CML 的进展中表现出多种功能。
