EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells.
Animals
Carcinogenesis
/ genetics
Carcinoma, Non-Small-Cell Lung
/ genetics
Cell Line
Cell Proliferation
/ genetics
Cellular Senescence
/ genetics
DNA Damage
Disease Models, Animal
Epithelial Cells
Female
Fibroblasts
Gene Expression Regulation, Neoplastic
Genetic Vectors
/ genetics
Humans
Lentivirus
/ genetics
Lung Neoplasms
/ genetics
Mice
Oncogene Proteins, Fusion
/ genetics
RNA-Seq
Telomerase
/ genetics
Telomere Homeostasis
/ genetics
Transfection
Anchorage-independent growth
DNA damage
EML4-ALK
Lung cancer
Senescence
hTERT
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
24 Mar 2021
24 Mar 2021
Historique:
received:
13
06
2020
accepted:
12
02
2021
entrez:
25
3
2021
pubmed:
26
3
2021
medline:
4
5
2021
Statut:
epublish
Résumé
Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells. Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes. The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16 Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression.
Sections du résumé
BACKGROUND
BACKGROUND
Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.
METHODS
METHODS
Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes.
RESULTS
RESULTS
The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16
CONCLUSIONS
CONCLUSIONS
Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression.
Identifiants
pubmed: 33761896
doi: 10.1186/s12885-021-07905-6
pii: 10.1186/s12885-021-07905-6
pmc: PMC7992817
doi:
Substances chimiques
EML4-ALK fusion protein, human
0
Oncogene Proteins, Fusion
0
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
310Subventions
Organisme : NCI NIH HHS
ID : Intramural funds
Pays : United States
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