TY  - JOUR
AU  - Larribère, Lionel
AU  - Kuphal, Silke
AU  - Sachpekidis, Christos
AU  - Hüser, Laura
AU  - Bosserhoff, Anja
AU  - Utikal, Jochen
TI  - Targeted Therapy-Resistant Melanoma Cells Acquire Transcriptomic Similarities with Human Melanoblasts.
JO  - Cancers
VL  - 10
IS  - 11
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2018-02302
SP  - 451
PY  - 2018
AB  - The mechanisms of adaptive and acquired drug resistance in tumors are not completely understood. So far, gene amplifications or mutations, leading to the reactivation of the MAPK or PI3K pathways have been described. In this study, we used two different methods to generate human melanoblasts: (1) via differentiation from induced pluripotent stem cells (iPSCs) and (2) via dedifferentiation from melanocytes. The melanoblast transcriptomes were then compared to the transcriptome of MAPK inhibitor-resistant melanoma cells. We observed that the expression of genes associated with cell cycle control, DNA damage control, metabolism, and cancer was altered in both melanoblast populations and in both adaptive and acquired resistant melanoma samples, compared to drug-sensitive samples. However, genes involved in antigen presentation and cellular movement were only regulated in the melanoblast populations and in the acquired resistant melanoma samples, compared to the drug-sensitive samples. Moreover, melanocyte-derived melanoblasts and adaptive resistant melanoma samples were characterized by different expression levels of certain transcription factors or genes involved in the CDK5 pathway. In conclusion, we show here that in vitro models of human melanoblasts are very important tools to comprehend the expression profiles of drug-resistant melanoma.
LB  - PUB:(DE-HGF)16
C6  - pmid:30453548
C2  - pmc:PMC6265976
DO  - DOI:10.3390/cancers10110451
UR  - https://inrepo02.dkfz.de/record/142072
ER  -