- Title
- RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors
- Creator
- Lei, Fu Xi; Jin, Lei; Liu, Xiao Ying; Lai, Fritz; Yan, Xu Guang; Farrelly, Margaret; Guo, Su Tang; Zhao, Xin Han; Zhang, Xu Dong
- Relation
- Cell Death and Disease Vol. 9, Issue 6
- Publisher Link
- http://dx.doi.org/10.1038/s41419-018-0714-7
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2018
- Description
- Many recent studies have uncovered the necessary role for the receptor-interacting protein kinase 1 (RIP1) in regulating apoptosis and necrosis that cells undergo in response to various cellular stresses. However, the functional significance of RIP1 in promoting cancer cells survival remains poorly understood. Here, we report that RIP1 was upregulated and contributed to both intrinsic and acquired resistance of melanoma cells to BRAF/MEK inhibitors through activation of NF-κB. Strikingly, Snail1-mediated suppression of CYLD played a crucial role in promoting RIP1 expression upon ERK activation, particularly, in melanoma cells with acquired resistance to BRAF inhibitors. In addition, RIP1 kinase activity was not required for melanoma cells to survive BRAF/MEK inhibition as RIP1 mediated NF-κB activation through its intermediate domain. Collectively, our findings reveal that targeting RIP1 in combination with BRAF/MEK inhibitors is a potential approach in the treatment of the disease.
- Subject
- RIP1; receptor-interacting; melanoma; patient care; mutation
- Identifier
- http://hdl.handle.net/1959.13/1414549
- Identifier
- uon:36768
- Identifier
- ISSN:2041-4889
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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