Abstract
Since the very first moment of its discovery in 1996 [1], the FHIT (Fragile Histidine Triad) gene product appeared as a very intriguing molecule to be investigated in the pathogenesis of cancer. In fact, FHIT encompasses the most common fragile site in human [2], whose genetic alterations, leading to the loss of FHIT expression, have been reported in the majority of human cancers [3]. Other than genetic lesions, FHIT expression in both solid and hematopoietic malignancies is also impaired by its promoter hypermethylation [4, 5], making Fhit protein virtually completely lost in tumors. Moreover, several reports have intriguingly pointed to Fhit loss as a very early event in epithelial tumorigenesis (presumably, the earliest event in smoking-related lung cancer) [3].
Highlights
Since the very first moment of its discovery in 1996 [1], the FHIT (Fragile Histidine Triad) gene product appeared as a very intriguing molecule to be investigated in the pathogenesis of cancer
FHIT expression in both solid and hematopoietic malignancies is impaired by its promoter hypermethylation [4, 5], making Fhit protein virtually completely lost in tumors
We proved that the Fhit mutants able to bind the substrate but with impaired catalytic activity could still efficiently trigger apoptosis of cancer cells; apoptosis was still observed with Fhit mutants unable to bind the substrate, even though to a much lower extent compared to the wild-type protein [15, 16], suggesting that Fhit tumor suppression activity in cancer cells could presumably be dependent by different and independent molecular pathways
Summary
Since the very first moment of its discovery in 1996 [1], the FHIT (Fragile Histidine Triad) gene product appeared as a very intriguing molecule to be investigated in the pathogenesis of cancer. We proved that the Fhit mutants able to bind the substrate but with impaired catalytic activity could still efficiently trigger apoptosis of cancer cells; apoptosis was still observed with Fhit mutants unable to bind the substrate, even though to a much lower extent compared to the wild-type protein [15, 16], suggesting that Fhit tumor suppression activity in cancer cells could presumably be dependent by different and independent molecular pathways.
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