MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2
MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2
复制标题
MAP3K10通过上调Gli-1和Gli-2促进胰腺癌细胞增殖并降低对吉西他滨的敏感性
DOI：
10.1016/j.canlet.2012.11.005
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发表时间：
2013-02-28
期刊：
影响因子：
9.7
通讯作者：
Miao, Yi
中科院分区：
文献类型：
--
作者：
An, Yong;Cai, Baobao;Miao, Yi
胰腺导管腺癌 (PDAC) 是最致命的人类恶性肿瘤之一，受 Sonic Hedgehog (Shh) 信号传导调节。最近，MAP3K10 已被证明可以调节 Shh 信号传导，表明 MAP3K10 在 PDAC 肿瘤发生中发挥作用。我们测定了 PDAC 组织和细胞系中 MAP3K10 的表达状态，并在体外分析了 MAP3K10 过表达或敲低的 PDAC 细胞的活力和细胞增殖。 MAP3K10 在 PDAC 组织和细胞系中表达上调。 MAP3K10的过度表达促进胰腺癌细胞的增殖并降低吉西他滨的敏感性。相反，敲低 MAP3K10 显着降低细胞增殖并使细胞对吉西他滨敏感。然而，MAP3K10 的过度表达和敲低均不影响细胞迁移。此外，MAP3K10 的过度表达导致 PDAC 细胞中 Gli-1 和 Gli-2 的上调。我们的结果表明 MAP3K10 在 PDAC 的增殖和化疗耐药性中具有新颖且重要的作用。我们的研究表明，靶向 MAP3K10 是开发胰腺癌替代疗法的潜在策略。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal human malignancies and is regulated by Sonic Hedgehog (Shh) signaling. Recently, MAP3K10 has been shown to regulate Shh signaling, suggesting a role for MAP3K10 in the tumorigenesis of PDAC. We determined the expression status of MAP3K10 in PDAC tissues and cell lines, and analyzed the viability and cell proliferation of PDAC cells with an overexpression or knockdown of MAP3K10 in vitro. MAP3K10 was upregulated in PDAC tissues and cell lines. Overexpression of MAP3K10 promoted the proliferation and decreased the gemcitabine sensitivity of pancreatic cancer cells. In contrast, knockdown of MAP3K10 significantly decreased cell proliferation and sensitized cells to gemcitabine. However, neither overexpression nor knockdown of MAP3K10 affected cell migration. Moreover, overexpression of MAP3K10 resulted in upregulation of Gli-1 and Gli-2 in PDAC cells. Our results indicate a novel and important role for MAP3K10 in the proliferation and chemoresistance of PDAC. Our study suggests that targeting MAP3K10 is a potential strategy for the development of alternative therapies for pancreatic cancers. (C) 2012 Elsevier Ireland Ltd. All rights reserved.