Pictilisib-Induced Resistance Is Mediated through FOXO1-Dependent Activation of Receptor Tyrosine Kinases in Mucinous Colorectal Adenocarcinoma Cells.
Humans
Phosphatidylinositol 3-Kinases
/ metabolism
Receptor Protein-Tyrosine Kinases
Forkhead Transcription Factors
/ metabolism
Adenocarcinoma
Phosphoinositide-3 Kinase Inhibitors
Colorectal Neoplasms
/ drug therapy
Tyrosine
Proto-Oncogene Proteins c-akt
/ metabolism
Forkhead Box Protein O1
/ genetics
FOXO
mucinous colorectal adenocarcinomas
pictilisib
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
02 Aug 2023
02 Aug 2023
Historique:
received:
07
07
2023
accepted:
25
07
2023
medline:
14
8
2023
pubmed:
12
8
2023
entrez:
12
8
2023
Statut:
epublish
Résumé
The phosphatidylinositol (PI3K)/AKT/mTOR axis represents an important therapeutic target to treat human cancers. A well-described downstream target of the PI3K pathway is the forkhead box O (FOXO) transcription factor family. FOXOs have been implicated in many cellular responses, including drug-induced resistance in cancer cells. However, FOXO-dependent acute phase resistance mediated by pictilisib, a potent small molecule PI3K inhibitor (PI3Ki), has not been studied. Here, we report that pictilisib-induced adaptive resistance is regulated by the FOXO-dependent rebound activity of receptor tyrosine kinases (RTKs) in mucinous colorectal adenocarcinoma (MCA) cells. The resistance mediated by PI3K inhibition involves the nuclear localization of FOXO and the altered expression of RTKs, including
Identifiants
pubmed: 37569713
pii: ijms241512331
doi: 10.3390/ijms241512331
pmc: PMC10418489
pii:
doi:
Substances chimiques
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
0
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Forkhead Transcription Factors
0
Phosphoinositide-3 Kinase Inhibitors
0
Tyrosine
42HK56048U
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Forkhead Box Protein O1
0
FOXO1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : BLRD VA
ID : I01 BX004127
Pays : United States
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