All roads lead to mTOR - Integrating inflammation and tumor angiogenesis
All roads lead to mTOR - Integrating inflammation and tumor angiogenesis
复制标题
DOI：
10.4161/cc.6.24.5085
复制
发表时间：
2007-12-15
期刊：
影响因子：
4.3
通讯作者：
Hung, Mien-Chie
中科院分区：
文献类型：
--
作者：
Lee, Dung-Fang;Hung, Mien-Chie
哺乳动物雷帕霉素靶蛋白（mTOR）是控制细胞大小和增殖的关键分子; mTOR通路的失调通常见于人类癌症。许多促癌激酶已被鉴定为通过磷酸化和TSC 1-TSC 2复合物失活的mTOR活性调节剂。肿瘤相关巨噬细胞（Tumor-associated macrophages，TAMs）是炎症介导的肿瘤发生发展中的促肿瘤因子，但TAMs介导的肿瘤血管生成中的信号分子尚不清楚。因此，迫切需要阐明炎症细胞和癌症之间的相互作用，并探索TAMs诱导肿瘤血管生成的确切途径。最近发现IKK β通过磷酸化TSC 1使TSC 1-TSC 2复合物失活来激活mTOR通路并促进肿瘤血管生成。这一发现为炎症介导的肿瘤血管生成提供了重要的见解，并提出了一种机制。在这个额外的视图中，我们简要地讨论了TAMs释放的促血管生成因子对mTOR激活的可能影响，并提出了肿瘤和TAMs在肿瘤血管生成中的串扰模型。
Mammalian target of rapamycin (mTOR) is a crucial molecule in the control of cell size and proliferation; dysregulation of the mTOR pathway is commonly found in human cancers. Many cancer-promoting kinases have been identified as regulators of mTOR activity through phosphorylation and inactivation of the TSC1-TSC2 complex. Tumor-associated macrophages (TAMs) are tumor-promoting factors in inflammation-mediated tumor development, and the signaling molecules involved in TAMs-mediated tumor angiogenesis are not well understood. Therefore, it is urgent to elucidate the cross-talk between inflammatory cells and cancers and to explore the precise pathways involved in TAMs-induced tumor angiogenesis. Recently IKK beta was found to activate the mTOR pathway and to promote tumor angiogenesis through inactivation of the TSC1 -TSC2 complex by phosphorylating TSC1. This finding provides critical insights into and suggests one mechanism behind inflammation-mediated tumor angiogenesis. In this extra-view, we briefly discuss the possible influence of TAMs-released proangiogenic factors on mTOR activation and propose a model of the cross-talk between tumors and TAMs in tumor angiogenesis.