AKT3 Expression in Mesenchymal Colorectal Cancer Cells Drives Growth and Is Associated with Epithelial-Mesenchymal Transition.
AKT3
CMS
growth
mesenchymal CRC
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
14 Feb 2021
14 Feb 2021
Historique:
received:
08
01
2021
revised:
05
02
2021
accepted:
09
02
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
7
3
2021
Statut:
epublish
Résumé
Colorectal cancer (CRC) is a heterogeneous disease that can currently be subdivided into four distinct consensus molecular subtypes (CMS) based on gene expression profiling. The CMS4 subtype is marked by high expression of mesenchymal genes and is associated with a worse overall prognosis compared to other CMSs. Importantly, this subtype responds poorly to the standard therapies currently used to treat CRC. We set out to explore what regulatory signalling networks underlie the CMS4 phenotype of cancer cells, specifically, by analysing which kinases were more highly expressed in this subtype compared to others. We found AKT3 to be expressed in the cancer cell epithelium of CRC specimens, patient derived xenograft (PDX) models and in (primary) cell cultures representing CMS4. Importantly, chemical inhibition or knockout of this gene hampers outgrowth of this subtype, as AKT3 controls expression of the cell cycle regulator p27
Identifiants
pubmed: 33673003
pii: cancers13040801
doi: 10.3390/cancers13040801
pmc: PMC7918753
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : KWF Kankerbestrijding
ID : UVA2014-7245
Organisme : KWF Kankerbestrijding
ID : 10150
Organisme : Oncode Institute
ID : n/a
Organisme : AMC Graduate School
ID : PhD Scholarship
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