FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7]
The inability of targeted BRAF inhibitors to produce long-lasting improvement in the clinical outcome of melanoma highlights a need to identify additional approaches to inhibit melanoma growth. Recent studies have shown that activation of the Wnt/β-catenin pathway decreases tumor growth and cooperat...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2013-10-01
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| Series: | F1000Research |
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| Online Access: | http://f1000research.com/articles/2-134/v2 |
| _version_ | 1819050655703105536 |
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| author | Willliam Conrad Michael B Major Michele A Cleary Marc Ferrer Brian Roberts Shane Marine Namjin Chung William T Arthur Randall T Moon Jason D Berndt Andy J Chien |
| author_facet | Willliam Conrad Michael B Major Michele A Cleary Marc Ferrer Brian Roberts Shane Marine Namjin Chung William T Arthur Randall T Moon Jason D Berndt Andy J Chien |
| author_sort | Willliam Conrad |
| collection | DOAJ |
| description | The inability of targeted BRAF inhibitors to produce long-lasting improvement in the clinical outcome of melanoma highlights a need to identify additional approaches to inhibit melanoma growth. Recent studies have shown that activation of the Wnt/β-catenin pathway decreases tumor growth and cooperates with ERK/MAPK pathway inhibitors to promote apoptosis in melanoma. Therefore, the identification of Wnt/β-catenin regulators may advance the development of new approaches to treat this disease. In order to move towards this goal we performed a large scale small-interfering RNA (siRNA) screen for regulators of β-catenin activated reporter activity in human HT1080 fibrosarcoma cells. Integrating large scale siRNA screen data with phosphoproteomic data and bioinformatics enrichment identified a protein, FAM129B, as a potential regulator of Wnt/β-catenin signaling. Functionally, we demonstrated that siRNA-mediated knockdown of FAM129B in A375 and A2058 melanoma cell lines inhibits WNT3A-mediated activation of a β-catenin-responsive luciferase reporter and inhibits expression of the endogenous Wnt/β-catenin target gene, AXIN2. We also demonstrate that FAM129B knockdown inhibits apoptosis in melanoma cells treated with WNT3A. These experiments support a role for FAM129B in linking Wnt/β-catenin signaling to apoptosis in melanoma. |
| first_indexed | 2024-12-21T11:51:30Z |
| format | Article |
| id | doaj.art-ff1f05613bc44720a0cd8e4b015f5057 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-21T11:51:30Z |
| publishDate | 2013-10-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-ff1f05613bc44720a0cd8e4b015f50572022-12-21T19:05:03ZengF1000 Research LtdF1000Research2046-14022013-10-01210.12688/f1000research.2-134.v22455FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7]Willliam Conrad0Michael B Major1Michele A Cleary2Marc Ferrer3Brian Roberts4Shane Marine5Namjin Chung6William T Arthur7Randall T Moon8Jason D Berndt9Andy J Chien10Department of Pharmacology, University of Washington School of Medicine, Seattle WA, 98195, USADepartment of Cell Biology and Physiology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill NC, 27599-7295, USAMerck & Co., Inc., West Point PA, 19486, USANCATS/NIH, Rockville MD, 20850, USAHudson Alpha Institute for Biotechnology, Huntsville AL, 35806, USADepartment of Screening and Protein Sciences, Merck Research Laboratories, North Wales PA, 19454, USABristol-Myers Squibb Company, Applied Genomics, Princeton NJ, 08543, USASeattle Genetics, Bothell WA, 98021, USAThe Institute for Stem Cell and Regenerative Medicine, Seattle WA, 98109, USAThe Institute for Stem Cell and Regenerative Medicine, Seattle WA, 98109, USAThe Institute for Stem Cell and Regenerative Medicine, Seattle WA, 98109, USAThe inability of targeted BRAF inhibitors to produce long-lasting improvement in the clinical outcome of melanoma highlights a need to identify additional approaches to inhibit melanoma growth. Recent studies have shown that activation of the Wnt/β-catenin pathway decreases tumor growth and cooperates with ERK/MAPK pathway inhibitors to promote apoptosis in melanoma. Therefore, the identification of Wnt/β-catenin regulators may advance the development of new approaches to treat this disease. In order to move towards this goal we performed a large scale small-interfering RNA (siRNA) screen for regulators of β-catenin activated reporter activity in human HT1080 fibrosarcoma cells. Integrating large scale siRNA screen data with phosphoproteomic data and bioinformatics enrichment identified a protein, FAM129B, as a potential regulator of Wnt/β-catenin signaling. Functionally, we demonstrated that siRNA-mediated knockdown of FAM129B in A375 and A2058 melanoma cell lines inhibits WNT3A-mediated activation of a β-catenin-responsive luciferase reporter and inhibits expression of the endogenous Wnt/β-catenin target gene, AXIN2. We also demonstrate that FAM129B knockdown inhibits apoptosis in melanoma cells treated with WNT3A. These experiments support a role for FAM129B in linking Wnt/β-catenin signaling to apoptosis in melanoma.http://f1000research.com/articles/2-134/v2Cell SignalingCellular Death & Stress ResponsesSkin Cancers (incl. Melanoma & Lymphoma) |
| spellingShingle | Willliam Conrad Michael B Major Michele A Cleary Marc Ferrer Brian Roberts Shane Marine Namjin Chung William T Arthur Randall T Moon Jason D Berndt Andy J Chien FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7] F1000Research Cell Signaling Cellular Death & Stress Responses Skin Cancers (incl. Melanoma & Lymphoma) |
| title | FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7] |
| title_full | FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7] |
| title_fullStr | FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7] |
| title_full_unstemmed | FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7] |
| title_short | FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells [v2; ref status: indexed, http://f1000r.es/1w7] |
| title_sort | fam129b is a novel regulator of wnt β catenin signal transduction in melanoma cells v2 ref status indexed http f1000r es 1w7 |
| topic | Cell Signaling Cellular Death & Stress Responses Skin Cancers (incl. Melanoma & Lymphoma) |
| url | http://f1000research.com/articles/2-134/v2 |
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