---
_id: '1848'
abstract:
- lang: eng
  text: 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.
article_processing_charge: No
article_type: original
author:
- first_name: Bettina
  full_name: Schwamb, Bettina
  last_name: Schwamb
- first_name: Robert
  full_name: Pick, Robert
  last_name: Pick
- first_name: Sara
  full_name: Fernández, Sara
  last_name: Fernández
- first_name: Kirsten
  full_name: Völp, Kirsten
  last_name: Völp
- first_name: Jan
  full_name: Heering, Jan
  last_name: Heering
- first_name: Volker
  full_name: Dötsch, Volker
  last_name: Dötsch
- first_name: Susanne
  full_name: Bösser, Susanne
  last_name: Bösser
- first_name: Jennifer
  full_name: Jung, Jennifer
  last_name: Jung
- first_name: Rasa
  full_name: Beinoravičiute Kellner, Rasa
  last_name: Beinoravičiute Kellner
- first_name: Josephine
  full_name: Wesely, Josephine
  last_name: Wesely
- first_name: Inka
  full_name: Zörnig, Inka
  last_name: Zörnig
- first_name: Matthias
  full_name: Hammerschmidt, Matthias
  last_name: Hammerschmidt
- first_name: Matthias
  full_name: Nowak, Matthias
  id: 30845DAA-F248-11E8-B48F-1D18A9856A87
  last_name: Nowak
- first_name: Roland
  full_name: Penzel, Roland
  last_name: Penzel
- first_name: Kurt
  full_name: Zatloukal, Kurt
  last_name: Zatloukal
- first_name: Stefan
  full_name: Joos, Stefan
  last_name: Joos
- first_name: Ralf
  full_name: Rieker, Ralf
  last_name: Rieker
- first_name: Abbas
  full_name: Agaimy, Abbas
  last_name: Agaimy
- first_name: Stephan
  full_name: Söder, Stephan
  last_name: Söder
- first_name: Kmarie
  full_name: Reid Lombardo, Kmarie
  last_name: Reid Lombardo
- first_name: Michael
  full_name: Kendrick, Michael
  last_name: Kendrick
- first_name: Michael
  full_name: Bardsley, Michael
  last_name: Bardsley
- first_name: Yujiro
  full_name: Hayashi, Yujiro
  last_name: Hayashi
- first_name: David
  full_name: Asuzu, David
  last_name: Asuzu
- first_name: Sabriya
  full_name: Syed, Sabriya
  last_name: Syed
- first_name: Tamás
  full_name: Ördög, Tamás
  last_name: Ördög
- first_name: Martin
  full_name: Zörnig, Martin
  last_name: Zörnig
citation:
  ama: Schwamb B, Pick R, Fernández S, et al. FAM96A is a novel pro-apoptotic tumor
    suppressor in gastrointestinal stromal tumors. <i>International Journal of Cancer</i>.
    2015;137(6):1318-1329. doi:<a href="https://doi.org/10.1002/ijc.29498">10.1002/ijc.29498</a>
  apa: Schwamb, B., Pick, R., Fernández, S., Völp, K., Heering, J., Dötsch, V., …
    Zörnig, M. (2015). FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal
    stromal tumors. <i>International Journal of Cancer</i>. Wiley. <a href="https://doi.org/10.1002/ijc.29498">https://doi.org/10.1002/ijc.29498</a>
  chicago: Schwamb, Bettina, Robert Pick, Sara Fernández, Kirsten Völp, Jan Heering,
    Volker Dötsch, Susanne Bösser, et al. “FAM96A Is a Novel Pro-Apoptotic Tumor Suppressor
    in Gastrointestinal Stromal Tumors.” <i>International Journal of Cancer</i>. Wiley,
    2015. <a href="https://doi.org/10.1002/ijc.29498">https://doi.org/10.1002/ijc.29498</a>.
  ieee: B. Schwamb <i>et al.</i>, “FAM96A is a novel pro-apoptotic tumor suppressor
    in gastrointestinal stromal tumors,” <i>International Journal of Cancer</i>, vol.
    137, no. 6. Wiley, pp. 1318–1329, 2015.
  ista: Schwamb B, Pick R, Fernández S, Völp K, Heering J, Dötsch V, Bösser S, Jung
    J, Beinoravičiute Kellner R, Wesely J, Zörnig I, Hammerschmidt M, Nowak M, Penzel
    R, Zatloukal K, Joos S, Rieker R, Agaimy A, Söder S, Reid Lombardo K, Kendrick
    M, Bardsley M, Hayashi Y, Asuzu D, Syed S, Ördög T, Zörnig M. 2015. FAM96A is
    a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors. International
    Journal of Cancer. 137(6), 1318–1329.
  mla: Schwamb, Bettina, et al. “FAM96A Is a Novel Pro-Apoptotic Tumor Suppressor
    in Gastrointestinal Stromal Tumors.” <i>International Journal of Cancer</i>, vol.
    137, no. 6, Wiley, 2015, pp. 1318–29, doi:<a href="https://doi.org/10.1002/ijc.29498">10.1002/ijc.29498</a>.
  short: B. Schwamb, R. Pick, S. Fernández, K. Völp, J. Heering, V. Dötsch, S. Bösser,
    J. Jung, R. Beinoravičiute Kellner, J. Wesely, I. Zörnig, M. Hammerschmidt, M.
    Nowak, R. Penzel, K. Zatloukal, S. Joos, R. Rieker, A. Agaimy, S. Söder, K. Reid
    Lombardo, M. Kendrick, M. Bardsley, Y. Hayashi, D. Asuzu, S. Syed, T. Ördög, M.
    Zörnig, International Journal of Cancer 137 (2015) 1318–1329.
date_created: 2018-12-11T11:54:20Z
date_published: 2015-09-01T00:00:00Z
date_updated: 2025-09-23T08:46:31Z
day: '01'
department:
- _id: LifeSc
doi: 10.1002/ijc.29498
external_id:
  isi:
  - '000357808900012'
  pmid:
  - '25716227'
intvolume: '       137'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497860/
month: '09'
oa: 1
oa_version: Submitted Version
page: 1318 - 1329
pmid: 1
publication: International Journal of Cancer
publication_status: published
publisher: Wiley
publist_id: '5253'
quality_controlled: '1'
scopus_import: '1'
status: public
title: FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal
  tumors
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 137
year: '2015'
...