Differential Functions of Splicing Factors in Mammary Transformation and Breast Cancer Metastasis.
MYC
SR protein
TRA2-beta
alternative RNA splicing
breast cancer
metastasis
splicing factor
triple negative breast cancer
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 11 2019
26 11 2019
Historique:
received:
03
07
2019
revised:
09
09
2019
accepted:
28
10
2019
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
21
10
2020
Statut:
ppublish
Résumé
Misregulation of alternative splicing is a hallmark of human tumors, yet to what extent and how it contributes to malignancy are only beginning to be unraveled. Here, we define which members of the splicing factor SR and SR-like families contribute to breast cancer and uncover differences and redundancies in their targets and biological functions. We identify splicing factors frequently altered in human breast tumors and assay their oncogenic functions using breast organoid models. We demonstrate that not all splicing factors affect mammary tumorigenesis in MCF-10A cells. Specifically, the upregulation of SRSF4, SRSF6, or TRA2β disrupts acinar morphogenesis and promotes cell proliferation and invasion in MCF-10A cells. By characterizing the targets of these oncogenic splicing factors, we identify shared spliced isoforms associated with well-established cancer hallmarks. Finally, we demonstrate that TRA2β is regulated by the MYC oncogene, plays a role in metastasis maintenance in vivo, and its levels correlate with breast cancer patient survival.
Identifiants
pubmed: 31775037
pii: S2211-1247(19)31443-3
doi: 10.1016/j.celrep.2019.10.110
pmc: PMC6936330
mid: NIHMS1544709
pii:
doi:
Substances chimiques
RNA Splicing Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2672-2688.e7Subventions
Organisme : NIGMS NIH HHS
ID : R43 GM116478
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA178206
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA013106
Pays : United States
Organisme : NIH HHS
ID : S10 OD020122
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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