Forkhead家族转录因子FoxM1与肿瘤

Forkhead family transcription factor FoxM1 and tumor

目的随着分子生物学和分子肿瘤学的深入研究,运用肿瘤发生发展中的关键分子做为诊断标志和治疗靶点已成为肿瘤诊治的新趋势。本研究旨在分析Forkhead家族转录因子FoxM1介导肿瘤发生发展的机制及其在分子诊断和靶向干预中的价值。方法应用PubMed及CNKI期刊全文数据库检索系统,以"FoxM1和肿瘤"为关键词,检索2011-03-2016-02的所有相关文献,共检索到英文文献383篇,中文文献97篇。纳入标准:(1)FoxM1介导肿瘤发生发展的机制;(2)FoxM1与肿瘤分子诊断及靶向干预。根据纳入标准,符合分析的文献44篇。结果 FoxM1通过调控细胞周期G1/S和G2/M期促转化分子Skp2、Cks1、C-myc和细胞周期调节分子Cdc25A、Cdc25B、Cyclin D1、p27kip1和p21cip1等表达,影响细胞有丝分裂、细胞周期、DNA损伤修复、细胞增殖与分化等生物学过程。FoxM1过表达导致细胞异常增殖、新生血管形成、上皮-间质转化、维持干细胞特性、代谢异常和细胞逃逸衰老等生物学表征,促进细胞恶性转化,参与肿瘤发生发展。FoxM1还可调节多种肿瘤细胞对药物敏感性与耐药性。基于FoxM1的恶性肿瘤诊断系统对多种早期癌症的诊断具有良好价值。以FoxM1为靶点的抗肿瘤化合物通过抑制肿瘤细胞中过度表达的FoxM1成为临床治疗的潜在的新策略。结论 FoxM1过表达促进肿瘤发生发展,检测FoxM1分子有助于肿瘤早期识别,抑制FoxM1可以靶向干预肿瘤的发生发展,FoxM1是肿瘤诊疗的潜在靶标。

OBJECTIVE With the development of molecular biology and molecular oncology, the use of key molecules which is important in development of tumor as diagnostic markers and therapeutic targets has become a new trend. This research summarizes the advancements in findings about FoxM1, the transcription factor belonging to the Forkhead family, this article explores the role of FoxM1 in tumorigenesis, development, molecular diagnosis and targeted therapy. METHODS A comprehensive search on PubMed and CNKI databases was performed with ＂FoxM1 and tumor＂ as key words to find all related manuscripts published from 2011-03 to 2016-02. A total of 383 articles in English and 97 articles in Chinese were collected. INCLUSION CRITERIA： Role of FoxM1 in tumorigenesis and tumor progression; Role of FoxM1 in diagnosis and targeted therapy of tumors. In total, 44 articles were selected according to the mentioned criteria. RESULTS The investigated articles show that FoxM1, the transcriptional factor which belongs to Foxhead superfamily, can affect multiple biological processes, such as cell mitosis, cell cycle, DNA damage repair, cell proliferation and differentiation. This result is achieved by regulating the expression of Skp2,Cksl and C-myc, all of which promote the transformation of G1 /S and G2/M, and the cell cycle regulators which include Cdc25A,Cdc25B, Cyclin D1, p27 kipl and p2 cipl. Literature also shows that overexpression of FoxM1 may lead to abnormal regulation of multiple aspects of cell proliferation, angiogenesis, epithelial-mesenchymal transition, maintaining characteristics of stem cells, metabolism and escape of senescence that promote cells malignant transformation and participate in the carcinogenesis and development. FoxM1 regulates drug sensitivity and resistance in a variety of tumor cells. Quantitative index diagnostic system based on expres- sion of FoxM1 show-s good accuracy in the early diagnosis of cancer. Anti-tumor compounds inhibit overexpressed FoxM1 and promote the process of FoxM1 as clinical therapeutic target. CONCLUSIONS Overexpression of FoxM1 plays an important role in carcinoma and development. The detection of FoxM1 may be helpful on early identification of tumorigenesis. The specific inhibition of FoxM1 can be targeted intervention of tumorigenesis and development; FoxM1 is a potential target for tumor diagnosis and treatment.