MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Carcinoma, Non-Small-Cell Lung
/ diagnostic imaging
Cell Line, Tumor
Cell Survival
/ drug effects
Clonal Evolution
DNA Copy Number Variations
Datasets as Topic
Disease Models, Animal
Disease Progression
Humans
Lung
/ diagnostic imaging
Lung Neoplasms
/ diagnostic imaging
Mice
Mice, Transgenic
Mutation
Myeloid Cell Leukemia Sequence 1 Protein
/ antagonists & inhibitors
Primary Cell Culture
Prospective Studies
Proto-Oncogene Proteins p21(ras)
/ genetics
Pyrimidines
/ pharmacology
RNA-Seq
Retrospective Studies
Spheroids, Cellular
Thiophenes
/ pharmacology
Tumor Burden
/ drug effects
Tumor Suppressor Protein p53
/ genetics
X-Ray Microtomography
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 09 2020
10 09 2020
Historique:
received:
01
11
2019
accepted:
20
08
2020
entrez:
11
9
2020
pubmed:
12
9
2020
medline:
2
10
2020
Statut:
epublish
Résumé
Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
Identifiants
pubmed: 32913197
doi: 10.1038/s41467-020-18372-1
pii: 10.1038/s41467-020-18372-1
pmc: PMC7484793
doi:
Substances chimiques
Antineoplastic Agents
0
MCL1 protein, human
0
Mcl1 protein, mouse
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Pyrimidines
0
S63845
0
TP53 protein, human
0
Thiophenes
0
Trp53 protein, mouse
0
Tumor Suppressor Protein p53
0
Hras protein, mouse
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
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
4527Subventions
Organisme : Wellcome Trust
ID : 211179/Z/18/Z
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
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