Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells
Human melanomas show oncogenic B-Raf mutations which activate the B-Raf/MKK/ERK cascade. We screened microarrays to identify cellular targets of this pathway, and found that genes upregulated by B-Raf/MKK/ERK showed highest association with cell cycle regulators, whereas genes downregulated were mos...
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2009
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238492/ |
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pubmed-32384922011-12-15 Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells Argast, Gretchen M. Croy, Carrie H. Couts, Kasey L. Zhang, Zhiyong Litman, Elizabeth Chan, Daniel C. Ahn, Natalie G. Article Human melanomas show oncogenic B-Raf mutations which activate the B-Raf/MKK/ERK cascade. We screened microarrays to identify cellular targets of this pathway, and found that genes upregulated by B-Raf/MKK/ERK showed highest association with cell cycle regulators, whereas genes downregulated were most highly associated with axon guidance genes, including plexin-semaphorin family members. Plexin B1 was strongly inhibited by MAP kinase signaling in melanoma cells and melanocytes. In primary melanoma cells, plexin B1 blocked tumorigenesis as measured by growth of colonies in soft agar, spheroids in extracellular matrix, and xenograft tumors. Tumor suppression depended on residues in the C-terminal domain of plexin B1 which mediate receptor GAP activity, and also correlated with AKT inhibition. Interestingly, the inhibitory response to plexin B1 was reduced or absent in cells from a matched metastatic tumor, suggesting that changes occur in metastatic cells which bypass the tumor suppressor mechanisms. Plexin B1 also inhibited cell migration, but this was seen in metastatic cells and not in matched primary cells. Thus, plexin B1 has tumor suppressor function in early-stage cells, while suppressing migration in late-stage cells. Our findings suggest that B-Raf/MKK/ERK provides a permissive environment for melanoma genesis by modulating plexin B1. 2009-06-01 2009-07-30 /pmc/articles/PMC3238492/ /pubmed/19483722 http://dx.doi.org/10.1038/onc.2009.133 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
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NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Argast, Gretchen M. Croy, Carrie H. Couts, Kasey L. Zhang, Zhiyong Litman, Elizabeth Chan, Daniel C. Ahn, Natalie G. |
| spellingShingle |
Argast, Gretchen M. Croy, Carrie H. Couts, Kasey L. Zhang, Zhiyong Litman, Elizabeth Chan, Daniel C. Ahn, Natalie G. Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells |
| author_facet |
Argast, Gretchen M. Croy, Carrie H. Couts, Kasey L. Zhang, Zhiyong Litman, Elizabeth Chan, Daniel C. Ahn, Natalie G. |
| author_sort |
Argast, Gretchen M. |
| title |
Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells |
| title_short |
Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells |
| title_full |
Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells |
| title_fullStr |
Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells |
| title_full_unstemmed |
Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells |
| title_sort |
plexin b1 is repressed by oncogenic b-raf signaling and functions as a tumor suppressor in melanoma cells |
| description |
Human melanomas show oncogenic B-Raf mutations which activate the B-Raf/MKK/ERK cascade. We screened microarrays to identify cellular targets of this pathway, and found that genes upregulated by B-Raf/MKK/ERK showed highest association with cell cycle regulators, whereas genes downregulated were most highly associated with axon guidance genes, including plexin-semaphorin family members. Plexin B1 was strongly inhibited by MAP kinase signaling in melanoma cells and melanocytes. In primary melanoma cells, plexin B1 blocked tumorigenesis as measured by growth of colonies in soft agar, spheroids in extracellular matrix, and xenograft tumors. Tumor suppression depended on residues in the C-terminal domain of plexin B1 which mediate receptor GAP activity, and also correlated with AKT inhibition. Interestingly, the inhibitory response to plexin B1 was reduced or absent in cells from a matched metastatic tumor, suggesting that changes occur in metastatic cells which bypass the tumor suppressor mechanisms. Plexin B1 also inhibited cell migration, but this was seen in metastatic cells and not in matched primary cells. Thus, plexin B1 has tumor suppressor function in early-stage cells, while suppressing migration in late-stage cells. Our findings suggest that B-Raf/MKK/ERK provides a permissive environment for melanoma genesis by modulating plexin B1. |
| publishDate |
2009 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238492/ |
| _version_ |
1611494214723436544 |