ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2.
CAM model
De-adhesion
EMT
Intratumoral heterogeneity
Liver metastasis
Migration
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
15 Jul 2022
15 Jul 2022
Historique:
received:
12
04
2022
accepted:
23
06
2022
revised:
21
06
2022
entrez:
15
7
2022
pubmed:
16
7
2022
medline:
20
7
2022
Statut:
epublish
Résumé
In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues. Immunostainings revealed that high intratumoral heterogeneity for ATF2 and TROP2 expression was sustained also in liver metastasis. Mechanistically, our in vitro data of CRISPR/Cas9-generated ATF2 knockout (KO) clones revealed that high TROP2 levels were critical for cell de-adhesion and increased cell migration without triggering EMT. TROP2 was enriched in filopodia and displaced Paxillin from adherens junctions. In vivo imaging, micro-computer tomography, and immunostainings verified that an ATF2
Identifiants
pubmed: 35838828
doi: 10.1007/s00018-022-04445-5
pii: 10.1007/s00018-022-04445-5
pmc: PMC9287261
doi:
Substances chimiques
ATF2 protein, human
0
Activating Transcription Factor 2
0
Antigens, Neoplasm
0
Cell Adhesion Molecules
0
TACSTD2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
423Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SCHN477/18-1
Organisme : European Cooperation in Science and Technology
ID : CA17118
Organisme : Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences
ID : LM2015040
Organisme : Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences
ID : RVO 68378050
Organisme : Univerzita Karlova v Praze
ID : Z.1.05/1.1.00/02.0109
Informations de copyright
© 2022. The Author(s).
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