Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response
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Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response. / Bernhardt, Mathias; Novak, Daniel; Assenov, Yassen; Orouji, Elias; Knappe, Nathalie; Weina, Kasia; Reith, Maike; Larribere, Lionel; Gebhardt, Christoffer; Plass, Christoph; Umansky, Viktor; Utikal, Jochen.
in: STEM CELL REP, Jahrgang 8, Nr. 5, 09.05.2017, S. 1379-1391.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response
AU - Bernhardt, Mathias
AU - Novak, Daniel
AU - Assenov, Yassen
AU - Orouji, Elias
AU - Knappe, Nathalie
AU - Weina, Kasia
AU - Reith, Maike
AU - Larribere, Lionel
AU - Gebhardt, Christoffer
AU - Plass, Christoph
AU - Umansky, Viktor
AU - Utikal, Jochen
N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2017/5/9
Y1 - 2017/5/9
N2 - A point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%-60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is circumvented by epigenetic mechanisms. Here, we mimicked epigenetic modifications in melanoma cells by reprogramming them into metastable induced pluripotent cancer cells (iPCCs) with the ability to terminally differentiate into non-tumorigenic lineages. iPCCs and their differentiated progeny were characterized by an increased resistance against targeted therapies, although the cells harbor the same oncogenic mutations and signaling activity as the parental melanoma cells. Furthermore, induction of a pluripotent state allowed the melanoma-derived cells to acquire a non-tumorigenic cell fate, further suggesting that tumorigenicity is influenced by the cell state.
AB - A point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%-60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is circumvented by epigenetic mechanisms. Here, we mimicked epigenetic modifications in melanoma cells by reprogramming them into metastable induced pluripotent cancer cells (iPCCs) with the ability to terminally differentiate into non-tumorigenic lineages. iPCCs and their differentiated progeny were characterized by an increased resistance against targeted therapies, although the cells harbor the same oncogenic mutations and signaling activity as the parental melanoma cells. Furthermore, induction of a pluripotent state allowed the melanoma-derived cells to acquire a non-tumorigenic cell fate, further suggesting that tumorigenicity is influenced by the cell state.
KW - Animals
KW - Antineoplastic Agents
KW - Carcinogenesis
KW - Cell Line
KW - Cell Lineage
KW - Cells, Cultured
KW - Cellular Reprogramming
KW - Epigenesis, Genetic
KW - Fibroblasts
KW - Humans
KW - Induced Pluripotent Stem Cells
KW - Melanoma
KW - Mice
KW - Mice, Inbred NOD
KW - Mice, SCID
KW - Neoplastic Stem Cells
KW - Neurons
KW - Oncogene Proteins
KW - Journal Article
U2 - 10.1016/j.stemcr.2017.03.007
DO - 10.1016/j.stemcr.2017.03.007
M3 - SCORING: Journal article
C2 - 28392221
VL - 8
SP - 1379
EP - 1391
JO - STEM CELL REP
JF - STEM CELL REP
SN - 2213-6711
IS - 5
ER -