Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells
Melanoma is the deadliest form of skin cancer and develops from the melanocytes that are responsible for the pigmentation of the skin. The skin is also a highly regenerative organ, harboring a pool of undifferentiated melanocyte stem cells that proliferate and differentiate into mature melanocytes d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1297910/full |
| _version_ | 1797629055586009088 |
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| author | Esra Katkat Esra Katkat Yeliz Demirci Yeliz Demirci Guillaume Heger Doga Karagulle Doga Karagulle Irene Papatheodorou Alvis Brazma Gunes Ozhan Gunes Ozhan |
| author_facet | Esra Katkat Esra Katkat Yeliz Demirci Yeliz Demirci Guillaume Heger Doga Karagulle Doga Karagulle Irene Papatheodorou Alvis Brazma Gunes Ozhan Gunes Ozhan |
| author_sort | Esra Katkat |
| collection | DOAJ |
| description | Melanoma is the deadliest form of skin cancer and develops from the melanocytes that are responsible for the pigmentation of the skin. The skin is also a highly regenerative organ, harboring a pool of undifferentiated melanocyte stem cells that proliferate and differentiate into mature melanocytes during regenerative processes in the adult. Melanoma and melanocyte regeneration share remarkable cellular features, including activation of cell proliferation and migration. Yet, melanoma considerably differs from the regenerating melanocytes with respect to abnormal proliferation, invasive growth, and metastasis. Thus, it is likely that at the cellular level, melanoma resembles early stages of melanocyte regeneration with increased proliferation but separates from the later melanocyte regeneration stages due to reduced proliferation and enhanced differentiation. Here, by exploiting the zebrafish melanocytes that can efficiently regenerate and be induced to undergo malignant melanoma, we unravel the transcriptome profiles of the regenerating melanocytes during early and late regeneration and the melanocytic nevi and malignant melanoma. Our global comparison of the gene expression profiles of melanocyte regeneration and nevi/melanoma uncovers the opposite regulation of a substantial number of genes related to Wnt signaling and transforming growth factor beta (TGF-β)/(bone morphogenetic protein) BMP signaling pathways between regeneration and cancer. Functional activation of canonical Wnt or TGF-β/BMP pathways during melanocyte regeneration promoted melanocyte regeneration but potently suppressed the invasiveness, migration, and proliferation of human melanoma cells in vitro and in vivo. Therefore, the opposite regulation of signaling mechanisms between melanocyte regeneration and melanoma can be exploited to stop tumor growth and develop new anti-cancer therapies. |
| first_indexed | 2024-03-11T10:48:00Z |
| format | Article |
| id | doaj.art-5f92aee756d64bd5b2de22225f6c8555 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-11T10:48:00Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-5f92aee756d64bd5b2de22225f6c85552023-11-13T19:17:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-11-011110.3389/fcell.2023.12979101297910Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cellsEsra Katkat0Esra Katkat1Yeliz Demirci2Yeliz Demirci3Guillaume Heger4Doga Karagulle5Doga Karagulle6Irene Papatheodorou7Alvis Brazma8Gunes Ozhan9Gunes Ozhan10Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, TürkiyeIzmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Izmir, TürkiyeIzmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, TürkiyeIzmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Izmir, TürkiyeÉcole Centrale de Nantes, Nantes, FranceIzmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, TürkiyeDepartment of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, TürkiyeEuropean Molecular Biology Laboratory—European Bioinformatics Institute (EMBL-EBI), Cambridge, United KingdomEuropean Molecular Biology Laboratory—European Bioinformatics Institute (EMBL-EBI), Cambridge, United KingdomIzmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, TürkiyeDepartment of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, TürkiyeMelanoma is the deadliest form of skin cancer and develops from the melanocytes that are responsible for the pigmentation of the skin. The skin is also a highly regenerative organ, harboring a pool of undifferentiated melanocyte stem cells that proliferate and differentiate into mature melanocytes during regenerative processes in the adult. Melanoma and melanocyte regeneration share remarkable cellular features, including activation of cell proliferation and migration. Yet, melanoma considerably differs from the regenerating melanocytes with respect to abnormal proliferation, invasive growth, and metastasis. Thus, it is likely that at the cellular level, melanoma resembles early stages of melanocyte regeneration with increased proliferation but separates from the later melanocyte regeneration stages due to reduced proliferation and enhanced differentiation. Here, by exploiting the zebrafish melanocytes that can efficiently regenerate and be induced to undergo malignant melanoma, we unravel the transcriptome profiles of the regenerating melanocytes during early and late regeneration and the melanocytic nevi and malignant melanoma. Our global comparison of the gene expression profiles of melanocyte regeneration and nevi/melanoma uncovers the opposite regulation of a substantial number of genes related to Wnt signaling and transforming growth factor beta (TGF-β)/(bone morphogenetic protein) BMP signaling pathways between regeneration and cancer. Functional activation of canonical Wnt or TGF-β/BMP pathways during melanocyte regeneration promoted melanocyte regeneration but potently suppressed the invasiveness, migration, and proliferation of human melanoma cells in vitro and in vivo. Therefore, the opposite regulation of signaling mechanisms between melanocyte regeneration and melanoma can be exploited to stop tumor growth and develop new anti-cancer therapies.https://www.frontiersin.org/articles/10.3389/fcell.2023.1297910/fullwound healingmelanomaproliferationdifferentiationmigrationepithelial-to-mesenchymal transition |
| spellingShingle | Esra Katkat Esra Katkat Yeliz Demirci Yeliz Demirci Guillaume Heger Doga Karagulle Doga Karagulle Irene Papatheodorou Alvis Brazma Gunes Ozhan Gunes Ozhan Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells Frontiers in Cell and Developmental Biology wound healing melanoma proliferation differentiation migration epithelial-to-mesenchymal transition |
| title | Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells |
| title_full | Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells |
| title_fullStr | Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells |
| title_full_unstemmed | Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells |
| title_short | Canonical Wnt and TGF-β/BMP signaling enhance melanocyte regeneration but suppress invasiveness, migration, and proliferation of melanoma cells |
| title_sort | canonical wnt and tgf β bmp signaling enhance melanocyte regeneration but suppress invasiveness migration and proliferation of melanoma cells |
| topic | wound healing melanoma proliferation differentiation migration epithelial-to-mesenchymal transition |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1297910/full |
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