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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="SEMBA_FHIT_TARGETS_UP" SYSTEMATIC_NAME="M14812" 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 &gt; 1" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="Human_RefSeq" CONTRIBUTOR="Leona Saunders" CONTRIBUTOR_ORG="MSigDB Team" DESCRIPTION_BRIEF="Genes up-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="NM_000088,NM_000332,NM_002156,NM_006820,NM_015364,NM_016816,NM_025217,NM_032888,NM_152405,NM_181291,NM_182965" MEMBERS_SYMBOLIZED="ATXN1,COL1A1,COL27A1,HSPD1,IFI44L,JMY,LY96,OAS1,SPHK1,ULBP2,WDR20" MEMBERS_EZID="10964,1277,133746,23643,3329,4938,6310,80328,85301,8877,91833" MEMBERS_MAPPING="NM_000088,COL1A1,1277|NM_000332,ATXN1,6310|NM_002156,HSPD1,3329|NM_006820,IFI44L,10964|NM_015364,LY96,23643|NM_016816,OAS1,4938|NM_025217,ULBP2,80328|NM_032888,COL27A1,85301|NM_152405,JMY,133746|NM_181291,WDR20,91833|NM_182965,SPHK1,8877" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Homo sapiens" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
