EFA6B regulates a stop signal for collective invasion in breast cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 04 2021
13 04 2021
Historique:
received:
26
12
2019
accepted:
18
03
2021
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
29
4
2021
Statut:
epublish
Résumé
Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.
Identifiants
pubmed: 33850160
doi: 10.1038/s41467-021-22522-4
pii: 10.1038/s41467-021-22522-4
pmc: PMC8044243
doi:
Substances chimiques
Guanine Nucleotide Exchange Factors
0
PSD4 protein, human
0
CDC42 protein, human
EC 3.6.5.2
cdc42 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2198Références
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