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

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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.