TGF-β signaling in liver and gastrointestinal cancers.

TGF-β signaling in liver and gastrointestinal cancers.
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肝脏和胃肠道癌中的TGF-β信号传导。

DOI:
10.1016/j.canlet.2016.03.033
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发表时间:
2016-09-01
期刊:
影响因子:
9.7
通讯作者:
Mishra, L.
Mishra, L.
中科院分区:
医学1区
文献类型:
--
作者:
Katz, L. H.;Likhter, M.;Jogunoori, W.;Belkin, M.;Ohshiro, K.;Mishra, L.

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转化生长因子-β(Transforming growth Factor-β,TGF- β)在肝癌和胃肠道肿瘤中起着重要而复杂的作用。这些包括许多不同的功能,如维持干细胞稳态,促进纤维化,免疫调节,作为肿瘤抑制剂和矛盾的是,作为肿瘤进展。然而,负责这些不同动作的开关的关键机制知之甚少,仍然是一个挑战。癌症基因组图谱(TCGA)分析和基因工程小鼠模型现在提供了一种综合方法来剖析TGF-β途径的这些多方面且依赖于背景的驱动作用。在这篇综述中,我们将讨论TGF-β信号转导的分子机制,重点是结直肠癌,胃癌,胰腺癌和肝癌。在过去的十年中,已经开发了针对TGF-β通路的新药,其中一些已在临床试验中证明有效。更好地了解TGF-β通路可能会提高我们靶向它的能力,从而为对抗这些致命癌症的医疗设备提供更多工具。
Transforming Growth Factor-β (TGF- β) plays crucial and complex roles in liver and gastrointestinal cancers. These include a multitude of distinct functions, such as maintaining stem cell homeostasis, promoting fibrosis, immune modulating, as a tumor suppressor and paradoxically, as a tumor progressor. However, key mechanisms for the switches responsible for these distinct actions are poorly understood, and remain a challenge. The Cancer Genome Atlas (TCGA) analyses and genetically engineered mouse models now provide an integrated approach to dissect these multifaceted and context-dependent driving roles of the TGF-β pathway. In this review, we will discuss the molecular mechanisms of TGF-β signaling, focusing on colorectal, gastric, pancreatic, and liver cancers. Novel drugs targeting the TGF-β pathway have been developed over the last decade, and some have proven effective in clinical trials. A better understanding of the TGF-β pathway may improve our ability to target it, thus providing more tools to the armamentarium against these deadly cancers.
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