TBX2 and TBX3: the special value for anticancer drug targets.
TBX2 and TBX3: the special value for anticancer drug targets.
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DOI：
10.1016/j.bbcan.2010.07.001
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
He ML
中科院分区：
文献类型：
--
作者：
Lu J;Li XP;Dong Q;Kung HF;He ML
TBX2和TBX3是转录因子T-box家族的成员，与胚胎发育密切相关。与大多数T-box家族成员不同，TBX2和TBX3是仅有的哺乳动物T-box因子，它们通过C-末端的抑制结构域发挥转录抑制因子的作用。除了在发育中的作用外，最近的证据表明，TBX2和TBX3在一些癌症中过表达，包括黑色素瘤、乳腺癌、肝癌、肺癌、胰腺癌、卵巢癌和宫颈癌。然而，关于这些T-box基因如何促进肿瘤发生的机制，我们知之甚少。Tbx2和Tbx3的上调抑制了p14ARF和p21CIP1的表达，并通过失活P53途径促进了衰老的旁路。Tbx2在功能上与pRb相互作用，pRb调节tbx2的功能特异性。另外，Tbx2是Wnt信号通路的参与者，而Tbx3是Wnt/β-catenin通路的下游靶点，而过表达的Tbx2和Tbx3抑制了E-钙粘蛋白的表达，这被认为是上皮性肿瘤细胞侵袭的先决条件。此外，研究表明，TBX2与Egr1相互作用，阻断多个下游肿瘤抑制因子。本文就其在肿瘤发生中的研究进展作一综述，并展望其在靶向抗癌药物开发中的特殊价值。
TBX2 and TBX3 are members of the T-box family of transcription factors, which are implicated in embryonic development. Unlike most members of the T-box family, TBX2 and TBX3 are the only mammalian T-box factors which function as transcriptional repressors, mediated by the repression domain in the C-terminal. In addition to a role in development, recent evidence suggests that TBX2 and TBX3 are overexpressed in a number of cancers, including melanoma, breast, liver, lung, pancreas, ovarian, and cervical cancers. However, there is little information about the mechanisms for how these T-box genes contribute to tumorigenesis. Upregulation of TBX2 and TBX3 suppresses the expression of p14ARF and p21CIP1 and promotes bypass of senescence through inactivation of p53 pathway. TBX2 functionally interacts with pRb, and pRb modulates TBX2 functional specificity. In addition, TBX2 is a player of Wnt signaling while TBX3 is a downstream target of the Wnt/beta-catenin pathway, and overexpression of TBX2 and TBX3 represses the expression of E-cadherin, which is demonstrated to be a prerequisite for epithelial tumor cell invasion. Moreover, TBX2 is shown to interact with EGR1 to block multiple downstream tumor suppressors. Here, we review the current knowledge on TBX2 and TBX3 in tumorigenesis and prospect their special value for development of target-based anticancer drugs.
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影响因子：
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