Optogenetic control of NOTCH1 signaling
Abstract 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 cel...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-022-00885-5 |
| _version_ | 1811256741628739584 |
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| author | Joanna Kałafut Jakub Czapiński Alicja Przybyszewska-Podstawka Arkadiusz Czerwonka Adrian Odrzywolski Cecilia Sahlgren Adolfo Rivero-Müller |
| author_facet | Joanna Kałafut Jakub Czapiński Alicja Przybyszewska-Podstawka Arkadiusz Czerwonka Adrian Odrzywolski Cecilia Sahlgren Adolfo Rivero-Müller |
| author_sort | Joanna Kałafut |
| collection | DOAJ |
| description | Abstract 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 |
| first_indexed | 2024-04-12T17:45:52Z |
| format | Article |
| id | doaj.art-1ae1335d10fe49398ddb79f9c774c978 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-12T17:45:52Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-1ae1335d10fe49398ddb79f9c774c9782022-12-22T03:22:40ZengBMCCell Communication and Signaling1478-811X2022-05-0120111410.1186/s12964-022-00885-5Optogenetic control of NOTCH1 signalingJoanna Kałafut0Jakub Czapiński1Alicja Przybyszewska-Podstawka2Arkadiusz Czerwonka3Adrian Odrzywolski4Cecilia Sahlgren5Adolfo Rivero-Müller6Department of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinFaculty of Science and Engineering, Biosciences, Åbo AkademiDepartment of Biochemistry and Molecular Biology, Medical University of LublinAbstract 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 Abstracthttps://doi.org/10.1186/s12964-022-00885-5OptogeneticsNotch signalingNOTCH1Light-activationBreast cancer |
| spellingShingle | Joanna Kałafut Jakub Czapiński Alicja Przybyszewska-Podstawka Arkadiusz Czerwonka Adrian Odrzywolski Cecilia Sahlgren Adolfo Rivero-Müller Optogenetic control of NOTCH1 signaling Cell Communication and Signaling Optogenetics Notch signaling NOTCH1 Light-activation Breast cancer |
| title | Optogenetic control of NOTCH1 signaling |
| title_full | Optogenetic control of NOTCH1 signaling |
| title_fullStr | Optogenetic control of NOTCH1 signaling |
| title_full_unstemmed | Optogenetic control of NOTCH1 signaling |
| title_short | Optogenetic control of NOTCH1 signaling |
| title_sort | optogenetic control of notch1 signaling |
| topic | Optogenetics Notch signaling NOTCH1 Light-activation Breast cancer |
| url | https://doi.org/10.1186/s12964-022-00885-5 |
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