Optogenetic control of NOTCH1 signaling.
Breast cancer
Light-activation
NOTCH1
Notch signaling
Optogenetics
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
18 05 2022
18 05 2022
Historique:
received:
09
12
2021
accepted:
19
04
2022
entrez:
18
5
2022
pubmed:
19
5
2022
medline:
21
5
2022
Statut:
epublish
Résumé
The Notch signaling pathway is a crucial regulator of cell differentiation as well as tissue organization, whose deregulation is linked to the pathogenesis of different diseases. NOTCH1 plays a key role in breast cancer progression by increasing proliferation, maintenance of cancer stem cells, and impairment of cell death. NOTCH1 is a mechanosensitive receptor, where mechanical force is required to activate the proteolytic cleavage and release of the Notch intracellular domain (NICD). We circumvent this limitation by regulating Notch activity by light. To achieve this, we have engineered an optogenetic NOTCH1 receptor (optoNotch) to control the activation of NOTCH1 intracellular domain (N1ICD) and its downstream transcriptional activities. Using optoNotch we confirm that NOTCH1 activation increases cell proliferation in MCF7 and MDA-MB-468 breast cancer cells in 2D and spheroid 3D cultures, although causing distinct cell-type specific migratory phenotypes. Additionally, optoNotch activation induced chemoresistance on the same cell lines. OptoNotch allows the fine-tuning, ligand-independent, regulation of N1ICD activity and thus a better understanding of the spatiotemporal complexity of Notch signaling. Video Abstract.
Identifiants
pubmed: 35585598
doi: 10.1186/s12964-022-00885-5
pii: 10.1186/s12964-022-00885-5
pmc: PMC9118860
doi:
Substances chimiques
NOTCH1 protein, human
0
Receptor, Notch1
0
Types de publication
Journal Article
Video-Audio Media
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67Informations de copyright
© 2022. The Author(s).
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