Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes
Mutational activation of the BRAF proto-oncogene in melanocytes reliably produces benign nevi (pigmented ‘moles’), yet the same change is the most common driver mutation in melanoma. The reason nevi stop growing, and do not progress to melanoma, is widely attributed to a cell-autonomous process of ‘...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/61026 |
| _version_ | 1811235940623974400 |
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| author | Rolando Ruiz-Vega Chi-Fen Chen Emaad Razzak Priya Vasudeva Tatiana B Krasieva Jessica Shiu Michael G Caldwell Huaming Yan John Lowengrub Anand K Ganesan Arthur D Lander |
| author_facet | Rolando Ruiz-Vega Chi-Fen Chen Emaad Razzak Priya Vasudeva Tatiana B Krasieva Jessica Shiu Michael G Caldwell Huaming Yan John Lowengrub Anand K Ganesan Arthur D Lander |
| author_sort | Rolando Ruiz-Vega |
| collection | DOAJ |
| description | Mutational activation of the BRAF proto-oncogene in melanocytes reliably produces benign nevi (pigmented ‘moles’), yet the same change is the most common driver mutation in melanoma. The reason nevi stop growing, and do not progress to melanoma, is widely attributed to a cell-autonomous process of ‘oncogene-induced senescence’. Using a mouse model of Braf-driven nevus formation, analyzing both proliferative dynamics and single-cell gene expression, we found no evidence that nevus cells are senescent, either compared with other skin cells, or other melanocytes. We also found that nevus size distributions could not be fit by any simple cell-autonomous model of growth arrest, yet were easily fit by models based on collective cell behavior, for example in which arresting cells release an arrest-promoting factor. We suggest that nevus growth arrest is more likely related to the cell interactions that mediate size control in normal tissues, than to any cell-autonomous, ‘oncogene-induced’ program of senescence. |
| first_indexed | 2024-04-12T12:00:48Z |
| format | Article |
| id | doaj.art-ebbfba30db8a42e8b8e4e0ad08a82c27 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:00:48Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ebbfba30db8a42e8b8e4e0ad08a82c272022-12-22T03:33:51ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.61026Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytesRolando Ruiz-Vega0Chi-Fen Chen1Emaad Razzak2Priya Vasudeva3Tatiana B Krasieva4Jessica Shiu5Michael G Caldwell6Huaming Yan7John Lowengrub8Anand K Ganesan9https://orcid.org/0000-0003-4944-9274Arthur D Lander10https://orcid.org/0000-0002-4380-5525Center for Complex Biological Systems, University of California, Irvine, Irvine, United States; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United StatesDepartment of Dermatology, University of California, Irvine, Irvine, United StatesCenter for Complex Biological Systems, University of California, Irvine, Irvine, United StatesDepartment of Dermatology, University of California, Irvine, Irvine, United StatesBeckman Laser Institute, University of California, Irvine, Irvine, United StatesDepartment of Dermatology, University of California, Irvine, Irvine, United StatesCenter for Complex Biological Systems, University of California, Irvine, Irvine, United StatesDepartment of Mathematics, University of California, Irvine, Irvine, United StatesCenter for Complex Biological Systems, University of California, Irvine, Irvine, United States; Department of Mathematics, University of California, Irvine, Irvine, United StatesCenter for Complex Biological Systems, University of California, Irvine, Irvine, United States; Department of Dermatology, University of California, Irvine, Irvine, United StatesCenter for Complex Biological Systems, University of California, Irvine, Irvine, United States; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States; Department of Biological Chemistry, University of California, Irvine, Irvine, United StatesMutational activation of the BRAF proto-oncogene in melanocytes reliably produces benign nevi (pigmented ‘moles’), yet the same change is the most common driver mutation in melanoma. The reason nevi stop growing, and do not progress to melanoma, is widely attributed to a cell-autonomous process of ‘oncogene-induced senescence’. Using a mouse model of Braf-driven nevus formation, analyzing both proliferative dynamics and single-cell gene expression, we found no evidence that nevus cells are senescent, either compared with other skin cells, or other melanocytes. We also found that nevus size distributions could not be fit by any simple cell-autonomous model of growth arrest, yet were easily fit by models based on collective cell behavior, for example in which arresting cells release an arrest-promoting factor. We suggest that nevus growth arrest is more likely related to the cell interactions that mediate size control in normal tissues, than to any cell-autonomous, ‘oncogene-induced’ program of senescence.https://elifesciences.org/articles/61026nevusmelanocytesbraf mutationoncogene induced senescencenevus mouse modelskin |
| spellingShingle | Rolando Ruiz-Vega Chi-Fen Chen Emaad Razzak Priya Vasudeva Tatiana B Krasieva Jessica Shiu Michael G Caldwell Huaming Yan John Lowengrub Anand K Ganesan Arthur D Lander Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes eLife nevus melanocytes braf mutation oncogene induced senescence nevus mouse model skin |
| title | Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes |
| title_full | Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes |
| title_fullStr | Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes |
| title_full_unstemmed | Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes |
| title_short | Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes |
| title_sort | dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes |
| topic | nevus melanocytes braf mutation oncogene induced senescence nevus mouse model skin |
| url | https://elifesciences.org/articles/61026 |
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