A role of activated Sonic hedgehog signaling for the cellular proliferation of oral squamous cell carcinoma cell line.
A role of activated Sonic hedgehog signaling for the cellular proliferation of oral squamous cell carcinoma cell line.
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DOI：
10.1016/j.bbrc.2003.12.097
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发表时间：
2004-02
影响因子：
3.1
通讯作者：
Haruaki Nishimaki;K. Kasai;K. Kozaki;T. Takeo;H. Ikeda;S. Saga;M. Nitta;G. Itoh
中科院分区：
文献类型：
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作者：
Haruaki Nishimaki;K. Kasai;K. Kozaki;T. Takeo;H. Ikeda;S. Saga;M. Nitta;G. Itoh
Sonic Hedgehog(Shh)是一种分泌型的形态原，在哺乳动物发育过程中对适当的细胞增殖至关重要。Shh信号被激活后易发生在髓母细胞瘤和基底细胞癌等人类肿瘤中，而Shh信号在其他常见肿瘤中的作用仍存在争议。在这里，我们显示了Shh在14个口腔鳞状细胞癌(OSCC)细胞系中的5个细胞系中过表达。表达Shh的口腔鳞状细胞癌细胞系之一HSQ-显示，环多巴胺抑制细胞内Shh信号转导，抑制G1/S转换和细胞死亡。此外，我们发现Rho相关激酶的特异性抑制剂Y-27632处理可以模拟环多巴胺对HSQ-89细胞周期进程的影响。我们的研究揭示了激活的Shh信号参与了口腔鳞癌细胞的增殖，提示Shh信号可能是口腔鳞癌的一个良好的治疗靶点。
Sonic hedgehog (Shh) is a secreted morphogen crucial for appropriate cellular proliferation during mammalian development. The activated Shh signaling is known to predispose to human tumors such as medulloblastoma and basal cell carcinoma, while a role of Shh signaling in the other common tumors is still controversial. Here we showed the overexpression of Shh in five cell lines among 14 human oral squamous cell carcinoma (OSCC) cell lines. One of the Shh-expressing OSCC cell lines HSQ-89 showed the inhibition of G1/S transition and apoptotic cell death by treatment with Cyclopamine, a steroidal alkaloid that blocks the intracellular Shh signaling. Furthermore, we found that treatment with Y-27632, a specific inhibitor of Rho-associated kinase, mimicked the effect of Cyclopamine on the cell cycle progression of HSQ-89. Our study revealed the involvement of activated Shh signaling in the cellular proliferation of OSCC cells, indicating Shh signaling might be a good therapeutic target for OSCC.