Yanai Kosuke, Nakamura Masafumi, Akiyoshi Takashi, Nagai Shuntaro, Wada Junji, Koga Kenichiro, Noshiro Hirokazu, Nagai Eishi, Tsuneyoshi Masazumi, Tanaka Masao, Katano Mitsuo
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cancer Lett. 2008 May 8;263(1):145-56. doi: 10.1016/j.canlet.2007.12.030. Epub 2008 Feb 20.
Morphogenic signals like Hedgehog (Hh) and Wnt are reported to play critical roles in the progression of gastric cancer. We aimed to assess the relationship between Hh and Wnt signaling pathways. In 58 gastric cancer specimens, Wnt pathway activation was inversely correlated with Hh pathway activation. When AGS gastric cancer cells, in which Wnt signaling was constitutively active, were used as a target cell line, Gli1 overexpression suppressed Wnt transcriptional activity, nuclear beta-catenin accumulation and proliferation of AGS cells. Knock-down of beta-catenin by siRNA suppressed Wnt pathway activity and proliferation of AGS cells. Our data may provide some clues for the treatment of gastric cancer associated with Wnt signaling activation.
据报道，像刺猬信号通路（Hh）和Wnt这样的形态发生信号在胃癌进展中起关键作用。我们旨在评估Hh和Wnt信号通路之间的关系。在58份胃癌标本中，Wnt通路激活与Hh通路激活呈负相关。当将Wnt信号持续激活的AGS胃癌细胞用作靶细胞系时，Gli1过表达抑制了AGS细胞的Wnt转录活性、细胞核β-连环蛋白积累和增殖。通过小干扰RNA（siRNA）敲低β-连环蛋白可抑制Wnt通路活性和AGS细胞增殖。我们的数据可能为治疗与Wnt信号激活相关的胃癌提供一些线索。
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