Phosphoinositide 3-Kinase Signaling Can Modulate MHC Class I and II Expression.
Antigen Presentation
/ genetics
Binding Sites
/ genetics
Cell Proliferation
/ drug effects
DNA-Binding Proteins
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Genes, MHC Class I
/ genetics
Genes, MHC Class II
/ genetics
Genomics
Humans
Interferon-gamma
/ genetics
PTEN Phosphohydrolase
/ genetics
Phosphatidylinositol 3-Kinase
/ genetics
Protein Binding
/ genetics
Protein Kinase Inhibitors
/ pharmacology
Proto-Oncogene Proteins c-akt
/ genetics
STAT1 Transcription Factor
/ genetics
Signal Transduction
/ drug effects
Squamous Cell Carcinoma of Head and Neck
/ drug therapy
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
22
05
2019
revised:
06
08
2019
accepted:
17
09
2019
pubmed:
25
9
2019
medline:
23
6
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
Molecular events activating the PI3K pathway are frequently detected in human tumors and the activation of PI3K signaling alters numerous cellular processes including tumor cell proliferation, survival, and motility. More recent studies have highlighted the impact of PI3K signaling on the cellular response to interferons and other immunologic processes relevant to antitumor immunity. Given the ability of IFNγ to regulate antigen processing and presentation and the pivotal role of MHC class I (MHCI) and II (MHCII) expression in T-cell-mediated antitumor immunity, we sought to determine the impact of PI3K signaling on MHCI and MHCII induction by IFNγ. We found that the induction of cell surface MHCI and MHCII molecules by IFNγ is enhanced by the clinical grade PI3K inhibitors dactolisib and pictilisib. We also found that PI3K inhibition increases STAT1 protein levels following IFNγ treatment and increases accessibility at genomic STAT1-binding motifs. Conversely, we found that pharmacologic activation of PI3K signaling can repress the induction of MHCI and MHCII molecules by IFNγ, and likewise, the loss of PTEN attenuates the induction of MHCI, MHCII, and STAT1 by IFNγ. Consistent with these
Identifiants
pubmed: 31548239
pii: 1541-7786.MCR-19-0545
doi: 10.1158/1541-7786.MCR-19-0545
pmc: PMC7339488
mid: NIHMS1540520
doi:
Substances chimiques
DNA-Binding Proteins
0
IFNG protein, human
0
Protein Kinase Inhibitors
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
Interferon-gamma
82115-62-6
Phosphatidylinositol 3-Kinase
EC 2.7.1.137
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
PTEN Phosphohydrolase
EC 3.1.3.67
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2395-2409Subventions
Organisme : BLRD VA
ID : I01 BX001922
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207619
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000454
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA119338
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA160040
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA128613
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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