RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors.

Abstract:

: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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Lei FX,Jin L,Liu XY,Lai F,Yan XG,Farrelly M,Guo ST,Zhao XH,Zhang XD

doi

10.1038/s41419-018-0714-7

subject

Has Abstract

pub_date

2018-06-07 00:00:00

pages

679

issue

6

issn

2041-4889

pii

10.1038/s41419-018-0714-7

journal_volume

9

pub_type

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