Lu Juan, Li Xiang-Ping, Dong Qi, Kung Hsiang-Fu, He Ming-Liang
Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Biochim Biophys Acta. 2010 Dec;1806(2):268-74. doi: 10.1016/j.bbcan.2010.07.001. Epub 2010 Jul 17.
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 p14(ARF) and p21(CIP1) 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.
TBX2和TBX3是转录因子T盒家族的成员，它们与胚胎发育有关。与T盒家族的大多数成员不同，TBX2和TBX3是仅有的作为转录抑制因子发挥作用的哺乳动物T盒因子，由C端的抑制结构域介导。除了在发育中的作用外，最近的证据表明TBX2和TBX3在多种癌症中过表达，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盒基因如何促进肿瘤发生的机制知之甚少。TBX2和TBX3的上调抑制p14(ARF)和p21(CIP1)的表达，并通过p53途径的失活促进衰老的绕过。TBX2与pRb在功能上相互作用，pRb调节TBX2的功能特异性。此外，TBX2是Wnt信号的参与者，而TBX3是Wnt/β-连环蛋白途径的下游靶点，TBX2和TBX3的过表达抑制E-钙黏蛋白的表达，这被证明是上皮肿瘤细胞侵袭的先决条件。此外，TBX2显示与EGR1相互作用以阻断多个下游肿瘤抑制因子。在此，我们综述了目前关于TBX2和TBX3在肿瘤发生中的知识，并展望了它们在基于靶点的抗癌药物开发中的特殊价值。
