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SHR Neuro Krebs Kardio Lipid

Schwamb, B; Pick, R; Fernández, SB; Völp, K; Heering, J; Dötsch, V; Bösser, S; Jung, J; Beinoraviciute-Kellner, R; Wesely, J; Zörnig, I; Hammerschmidt, M; Nowak, M; Penzel, R; Zatloukal, K; Joos, S; Rieker, RJ; Agaimy, A; Söder, S; Reid-Lombardo, KM; Kendrick, ML; Bardsley, MR; Hayashi, Y; Asuzu, DT; Syed, SA; Ordog, T; Zörnig, M.
FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors.
Int J Cancer. 2015; 137(6):1318-1329 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Zatloukal Kurt

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Number of Figures: 6
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The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), "fibroblast-like cells" (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcription-polymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis. © 2015 UICC.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Apoptosis - genetics
Apoptotic Protease-Activating Factor 1 - genetics
Carrier Proteins - genetics
Cell Line -
Cell Line, Tumor -
Cell Transformation, Neoplastic - genetics
Gastrointestinal Stromal Tumors - genetics
Gene Expression - genetics
HEK293 Cells -
Humans -
Interstitial Cells of Cajal - metabolism
Mice -
Mice, Inbred NOD -
Mice, Nude -
Mice, SCID -
Mitochondria - genetics
Tumor Suppressor Proteins - genetics
Zebrafish - genetics

Find related publications in this database (Keywords)
tumor suppressor
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