摘要：近日来自天津医科大学的研究人员在国际著名期刊《肝脏病学》（Hepatology）（目前影响因子为10.84，在65种胃肠肝病学国际SCI杂志中位列第二）上发表了题为 “Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl-2 and Twist1: A study of hepatocellular carcinoma”的研究论文。
文章的通讯作者是著名病理学家孙保存教授，现任天津医科大学病理教研室主任，天津市肿瘤研究所副所长。其主要研究方向为肿瘤病理诊断和肿瘤血管生成，先后承担国家“863”计划、国家自然科学基金、教育部博士点基金和天津市科技发展重大攻关项目等课题15项。近年来发表论文200余篇，其中SCI收录27篇。论文先后在美国临床肿瘤年会和美国-加拿大病理学年会宣读，并被Nature review，Hepatology，Cancer Research等引用。
抗凋亡蛋白Bcl-2在细胞凋亡，免疫和自体吞噬中发挥多种作用。其在肿瘤中的表达与肿瘤的分级和恶性程度相关。正常发育的上皮-间质转化（EMT）过程的反复出现促成了肿瘤细胞的可塑性，其也是转移性细胞和血管生成拟态的特征。
在这篇文章中，研究人员解析了Bcl-2和EMT调节转录因子Twist1与肿瘤转移和血管生成拟态之间的关系，及两者在功能和结构的相互作用。研究人员证实BCL - 2和Twist1可在缺氧条件下共表达。在体内外实验中，研究人员证实BCL–2可与Twist1结合。这种相互作用与TWIST1的螺旋-环-螺旋DNA结合域有关，并通过Bcl - 2蛋白的两种单独结构域发生作用。 Bcl-2/Twist1复合物的形成有利于TWIST1的核转运，并可增加大范围肿瘤基因的激活，这些肿瘤基因与肿瘤细胞的形成，转移以及血管生成拟态密切相关。此外，研究人员还证实Bcl-2和Twist1的核表达与一项肝癌研究中97例患者的低生存率相关。
新研究表明Bcl-2在EMT诱导及肿瘤发展中起重要作用，并为研发新型化疗药物提供了Bcl-2/Twist1这一有潜力的治疗新靶点。
生物探索推荐英文论文摘要：
Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl‐2 and Twist1: A study of hepatocellular carcinoma
The antiapoptotic protein Bcl-2 plays multiple roles in apoptosis, immunity, and autophagy. Its expression in tumors correlates with tumor grade and malignancy. The recapitulation of the normal developmental process of epithelial-mesenchymal transition (EMT) contributes to tumor cell plasticity. This process is also a characteristic of metastatic cells and vasculogenic mimicry. In the present study we report functional and structural interactions between Bcl-2 and the EMT-regulating transcription factor Twist1 and the relationship with metastasis and vascular mimicry. Bcl-2 and Twist1 are coexpressed under hypoxia conditions. The Bcl-2 can bind to Twist1 in vivo and in vitro. This interaction involves basic helix-loop-helix DNA binding domain within Twist1 and through two separate domains within Bcl-2 protein. Formation of the Bcl-2/Twist1 complex facilitates the nuclear transport of Twist1 and leads to transcriptional activation of wide ranges of genes that can increase the tumor cell plasticity, metastasis, and vasculogenic mimicry. Finally, nuclear expression of Bcl-2 and Twist1 is correlated with poor survival of these patients in a cohort of 97 cases of human hepatocellular carcinoma. Conclusion: The results describe a novel function of Bcl-2 in EMT induction, provide insight into tumor progression, and implicate the Bcl-2/Twist1 complex as a potential target for developing chemotherapeutics.
