Fhit Tumor Suppressor: Guardian of the Preneoplastic Genome

Overview

Journal Future Oncol

Specialty Oncology

Date 2008 Dec 18

PMID 19086848

Citations 31

Authors

Flavia Pichiorri

Tiziana Palumbo

Sung-Suk Suh

Hiroshi Okamura

Francesco Trapasso

Hideshi Ishii

Kay Huebner

Carlo M Croce

Affiliations

Soon will be listed here.

Abstract

Environmental agents induce intragenic alterations in the FRA3B/FHIT chromosome fragile site, resulting in fragile FHIT allele loss early in cancer development. Fhit knockout mice are predisposed to tumor development and Fhit gene therapy reduces tumor burden. Repair-deficient cancers are likely to be Fhit-deficient and Fhit-deficient cells show enhanced resistance to ultraviolet C, mitomycin C, camptothecin and oxidative stress-induced cell killing. Loss of Fhit leads to alterations in the DNA damage response checkpoint and contributes to DNA instability. Hsp60/Hsp10 are Fhit interactors, suggesting a direct role for Fhit in stress responses. Fhit also interacts with and stabilizes ferrodoxin reductase (Fdxr), a mitochondrial flavoprotein that transfers electrons from NADPH to cytochrome P450, suggesting a role for Fhit in the modulation of reactive oxygen species production and of genomic damage.

Citing Articles

Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.

Tao S, Pu Y, Yang E, Ren G, Shi C, Chen L Exp Mol Med. 2025; 57(1):167-183.

PMID: 39762409 PMC: 11799392. DOI: 10.1038/s12276-024-01374-0.

Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.

Bellon M, Bialuk I, Galli V, Bai X, Farre L, Bittencourt A Mol Cancer. 2021; 20(1):86.

PMID: 34092254 PMC: 8183032. DOI: 10.1186/s12943-021-01370-2.

Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.

Chae H, Seo J, Kim S, Jeon Y, Suh S Int J Med Sci. 2021; 18(3):706-714.

PMID: 33437205 PMC: 7797533. DOI: 10.7150/ijms.51429.

Role of HSP60/HSP10 in Lung Cancer: Simple Biomarkers or Leading Actors?.

Fucarino A, Pitruzzella A J Oncol. 2020; 2020:4701868.

PMID: 32318107 PMC: 7149434. DOI: 10.1155/2020/4701868.

Impact of FHIT loss on the translation of cancer-associated mRNAs.

Kiss D, Baez W, Huebner K, Bundschuh R, Schoenberg D Mol Cancer. 2017; 16(1):179.

PMID: 29282095 PMC: 5745650. DOI: 10.1186/s12943-017-0749-x.

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