Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Br J Cancer. 2011 Jul 26;105(3):407-12. doi: 10.1038/bjc.2011.246. Epub 2011 Jul 5.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in response to growth factors and cytokines, and which contributes to the regulation of cell proliferation, apoptosis, and motility in many human tumour types.
We investigated the mechanisms of STAT3 activation and the function of STAT3 depending on its mechanism of activation in gastric cancer cells.
The MET-tyrosine kinase inhibitor (TKI) and cell transfection with a small interfering RNA (siRNA) specific for MET mRNA inhibited STAT3 phosphorylation in MET-activated cells, indicating that STAT3 activation is linked to MET signalling. Forced expression of a constitutively active form of STAT3 also attenuated MET-TKI-induced apoptosis, suggesting that inhibition of STAT3 activity contributes to MET-TKI-induced apoptosis. MKN1 and MKN7 cells, both of which are negative for MET activation, produced interleukin-6 (IL-6) that activated STAT3 through the Janus kinase pathway. Depletion of STAT3 by siRNA inhibited migration and invasion of these cells, suggesting that STAT3 activated by IL-6 contributes to regulation of cell motility.
Our data thus show that activated STAT3 contributes to either cell survival or motility in gastric cancer cells, and that these actions are related to different mechanisms of STAT3 activation.
信号转导子和转录激活子 3（STAT3）是一种转录因子，可响应生长因子和细胞因子而被激活，有助于调节多种人类肿瘤类型中的细胞增殖、凋亡和运动。
我们研究了胃癌细胞中 STAT3 激活的机制及其激活机制的功能。
MET 酪氨酸激酶抑制剂（TKI）和针对 MET mRNA 的小干扰 RNA（siRNA）的细胞转染抑制了 MET 激活细胞中 STAT3 的磷酸化，表明 STAT3 激活与 MET 信号有关。强制表达组成型激活形式的 STAT3 也减弱了 MET-TKI 诱导的细胞凋亡，表明抑制 STAT3 活性有助于 MET-TKI 诱导的细胞凋亡。MKN1 和 MKN7 细胞均未激活 MET，但产生白细胞介素 6（IL-6），通过 Janus 激酶途径激活 STAT3。用 siRNA 耗尽 STAT3 抑制了这些细胞的迁移和侵袭，表明 IL-6 激活的 STAT3 有助于调节细胞运动。
因此，我们的数据表明，激活的 STAT3 有助于胃癌细胞的细胞存活或运动，这些作用与 STAT3 激活的不同机制有关。
