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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="SEMBA_FHIT_TARGETS_DN" SYSTEMATIC_NAME="M10504" HISTORICAL_NAMES="" PMID="16407838" AUTHORS="Semba S,Trapasso F,Fabbri M,McCorkell KA,Volinia S,Druck T,Iliopoulos D,Pekarsky Y,Ishii H,Garrison PN,Barnes LD,Croce CM,Huebner K" GEOID="" EXACT_SOURCE="Table 1: Fold change &lt; 1" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="HUMAN_SEQ_ACCESSION" CONTRIBUTOR="Leona Saunders" CONTRIBUTOR_ORG="MSigDB Team" DESCRIPTION_BRIEF="Genes down-regulated in H1299 cells (non-small cell lung cancer, NSCLC) expressing the Y144F mutant form of FHIT [GeneID=2272]." DESCRIPTION_FULL="The Fhit tumor suppressor binds and hydrolyses diadenosine polyphosphates and the Fhit-substrate complex has been proposed as a proapoptotic effector, as determined by infection of susceptible cancer cells with adenoviruses carrying wild-type fragile histidine triad (FHIT) or catalytic site mutants. The highly conserved Fhit tyrosine 114 (Y114), within the unstructured loop C-terminal of the catalytic site, can be phosphorylated by Src family tyrosine kinases, although endogenous phospho-Fhit is rarely detected. To explore the importance of Y114 and identify Fhit-mediated signaling events, wild-type and Y114 mutant FHIT-expressing adenoviruses were introduced into two human lung cancer cell lines. Caspase-dependent apoptosis was effectively induced only by wild-type but not Y114 mutant Fhit proteins. By expression profiling of FHIT versus mutant FHIT-infected cells, we found that survivin, an Inhibitor of Apoptosis Protein (IAP) family member, was significantly decreased by wild-type Fhit. In addition, Fhit inhibited activity of Akt, a key effector in the phosphatidylinositol 3-OH kinase (PI3K) pathway; loss of endogenous Fhit expression caused increased Akt activity in vitro and in vivo, and overexpression of constitutively active Akt inhibited Fhit-induced apoptosis. The results indicate that the Fhit Y114 residue plays a critical role in Fhit-induced apoptosis, occurring through inactivation of the PI3K-Akt-survivin signal pathway." TAGS="" MEMBERS="BC019922,NM_001168,NM_006461,NM_012145,NM_014264,NM_016343,NM_017882,NM_018098,NM_018136,NM_018365" MEMBERS_SYMBOLIZED="ASPM,BIRC5,CENPF,CLN6,DTYMK,ECT2,MNS1,PLK4,SPAG5,ZNF252P" MEMBERS_EZID="10615,1063,10733,1841,1894,259266,286101,332,54982,55329" MEMBERS_MAPPING="BC019922,ZNF252P,286101|NM_001168,BIRC5,332|NM_006461,SPAG5,10615|NM_012145,DTYMK,1841|NM_014264,PLK4,10733|NM_016343,CENPF,1063|NM_017882,CLN6,54982|NM_018098,ECT2,1894|NM_018136,ASPM,259266|NM_018365,MNS1,55329" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Homo sapiens" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
