Notch signaling activation induces cell death in MAPKi-resistant melanoma cells.

ABSTRACT: The role of Notch signaling in melanoma drug resistance is not well understood. In this study, we show that although NOTCH proteins are upregulated in metastatic melanoma cell lines, Notch signaling inhibition had no effect on cell survival, growth, migration or the sensitivity of BRAFV600E-melanoma cells to MAPK inhibition (MAPKi). We found that NOTCH1 is downregulated in melanoma cell lines with intrinsic and acquired resistance to MAPKi. Forced expression of NICD1, the active form of Notch1, caused apoptosis of the NOTCH^lo , MAPKi-resistant cells, but not the NOTCH^hi , MAPKi-sensitive melanoma cell lines. Whole transcriptome-sequencing analyses of NICD1-transduced MAPKi-sensitive and MAPKi-resistant cells revealed differential regulation of endothelin 1 (EDN1) by N

SUBMITTER: Mikheil DM 

PROVIDER: S-EPMC6581614 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature