The Splicing Factor SF2 Is Critical for Hyperproliferation and Survival in a TORC1-Dependent Model of Early Tumorigenesis in Drosophila
dc.contributor.author
Parniewska, Malgorzata Maria
dc.contributor.author
Stocker, Hugo
dc.date.accessioned
2020-07-16T09:30:43Z
dc.date.available
2020-07-11T03:07:02Z
dc.date.available
2020-07-16T09:30:43Z
dc.date.issued
2020-06
dc.identifier.issn
1422-0067
dc.identifier.other
10.3390/ijms21124465
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/425926
dc.identifier.doi
10.3929/ethz-b-000425926
dc.description.abstract
The Target of Rapamycin complex 1 (TORC1) is an evolutionarily conserved kinase complex coordinating cellular growth with nutritional conditions and growth factor signaling, and its activity is elevated in many cancer types. The use of TORC1 inhibitors as anticancer drugs is, however, limited by unwanted side-effects and development of resistance. We therefore attempted to identify limiting modulators or downstream effectors of TORC1 that could serve as therapeutic targets. Drosophila epithelial tissues that lack the tumor suppressor Pten hyperproliferate upon nutrient restriction in a TORC1-dependent manner. We probed candidates of the TORC1 signaling network for factors limiting the overgrowth of Pten mutant tissues. The serine/arginine-rich splicing factor 2 (SF2) was identified as the most limiting factor: SF2 knockdown drives Pten mutant cells into apoptosis, while not affecting control tissue. SF2 acts downstream of or in parallel to TORC1 but is not required for the activation of the TORC1 target S6K. Transcriptomics analysis revealed transcripts with alternatively used exons regulated by SF2 in the tumor context, including p53. SF2 may therefore represent a highly specific therapeutic target for tumors with hyperactive TORC1 signaling.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
MDPI
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
TORC1
en_US
dc.subject
Cancer
en_US
dc.subject
Tumor suppression
en_US
dc.subject
SF2
en_US
dc.subject
Drosophila melanogaster
en_US
dc.subject
Pten
en_US
dc.title
The Splicing Factor SF2 Is Critical for Hyperproliferation and Survival in a TORC1-Dependent Model of Early Tumorigenesis in Drosophila
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-06-24
ethz.journal.title
International Journal of Molecular Sciences
ethz.journal.volume
21
en_US
ethz.journal.issue
12
en_US
ethz.journal.abbreviated
Int. j. mol. sci.
ethz.pages.start
4465
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Analysis of early tumorigenic stages in Drosophila epithelia
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Basel
en_US
ethz.publication.status
published
en_US
ethz.grant.agreementno
166680
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projekte Lebenswissenschaften
ethz.date.deposited
2020-07-11T03:07:16Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-07-16T09:30:54Z
ethz.rosetta.lastUpdated
2022-03-29T02:40:06Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=The%20Splicing%20Factor%20SF2%20Is%20Critical%20for%20Hyperproliferation%20and%20Survival%20in%20a%20TORC1-Dependent%20Model%20of%20Early%20Tumorigenesis%20in%20Drosophi&rft.jtitle=International%20Journal%20of%20Molecular%20Sciences&rft.date=2020-06&rft.volume=21&rft.issue=12&rft.spage=4465&rft.issn=1422-0067&rft.au=Parniewska,%20Malgorzata%20Maria&Stocker,%20Hugo&rft.genre=article&rft_id=info:doi/10.3390/ijms21124465&
Files in this item
Publication type
-
Journal Article [131619]