A role of Tumor Suppressor Fhit Product in Cell Death, Survival and Carcinogenesis

在发现第一个位于染色体脆性部位的基因--位于FRA3B的FHIT基因--的12年多的时间和800多篇科学论文之后，关于FHIT基因的表达缺失为细胞带来的选择优势，仍然存在一些问题。FHIT基因是癌前病变和癌症中最常见的等位基因缺失的目标。这些问题包括如何通过FHIT基因的缺失或改变来阻止癌细胞的死亡，以及癌细胞如何在微环境中生存；FHIT蛋白可以通过对细胞外刺激的反应而被磷酸化。因此，这一概念是根据最近对该基因座的遗传和表观遗传改变的研究，并回顾通过功能研究发现的FHIT蛋白的生物学作用而考虑的。

More than 12 years and >800 scientific publications after the discovery of the first gene at a chromosome fragile site, the FHIT gene at FRA3B, there are still questions to pursue concerning the selective advantage conferred to cells by loss of expression of FHIT, the most frequent target of allele deletion in precancerous lesions and cancers. These questions include how the cell death of cancer cells are prohibited by deficiency or alterations of FHIT gene and cancer cells would survive in the microenvironment ; the Fhit protein can be phosphorylated though the response to extracellular stimuli. Thus this notion is considered in light of recent investigations of genetic and epigenetic alterations to the locus and in a retrospective consideration of biological roles of the Fhit protein discovered through functional studies.