Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim
Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim
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DOI：
10.1093/jb/mvq114
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发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Miyazono, Kohei
中科院分区：
文献类型：
--
作者：
Hoshino, Yukari;Katsuno, Yoko;Miyazono, Kohei
癌细胞在获得转移能力方面经历多步骤过程，并且不断暴露于诱导细胞凋亡的信号。癌细胞获得抗凋亡特性对于转移是重要的，并且最近的研究表明转化生长因子（TGF）-β促进某些类型的癌细胞的存活。在这里，我们发现在高转移性乳腺癌细胞中，JygMC（A）、JygMC（B）和4 T1，TGF-β配体以自分泌方式产生。在无血清条件下，TGF-β I型受体激酶抑制剂对内源性TGF-β信号传导的药理学抑制增加了JygMC（A）和JygMC（B）细胞中仅BH 3蛋白Bim（也称为Bcl 2样11）的表达，并引起凋亡性细胞死亡。我们还发现，在Foxc 1敲低的癌细胞中没有观察到TGF-β诱导Bim。这些发现表明，TGF-β通过TGF-β-Foxc 1-Bim通路在调节某些类型癌细胞的存活中起着至关重要的作用，并且TGF-β信号传导的特异性抑制剂可能在乳腺癌细胞中用作凋亡诱导剂。
Cancer cells undergo multi-step processes in obtaining the ability to metastasize, and are constantly exposed to signals that induce apoptosis. Acquisition of anti-apoptotic properties by cancer cells is important for metastasis, and recent studies suggest that transforming growth factor (TGF)-beta promotes the survival of certain types of cancer cells. Here, we found that in highly metastatic breast cancer cells, JygMC(A), JygMC(B) and 4T1, TGF-beta ligands were produced in autocrine fashion. Pharmacological inhibition of endogenous TGF-beta signalling by a TGF-beta type I receptor kinase inhibitor in serum-free conditions increased the expression of BH3-only protein, Bim (also known as Bcl2-like 11) in JygMC(A) and JygMC(B) cells, and caused apoptotic cell death. We also found that induction of Bim by TGF-beta was not observed in Foxc1 knocked-down cancer cells. These findings suggest that TGF-beta plays a crucial role in the regulation of survival of certain types of cancer cells through the TGF-beta-Foxc1-Bim pathway, and that specific inhibitors of TGF-beta signalling might be useful as apoptosis inducers in breast cancer cells.