PMID- 26668268
OWN - NLM
STAT- MEDLINE
DCOM- 20160718
LR  - 20211203
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 35
IP  - 5
DP  - 2016 Mar 1
TI  - Actin remodeling confers BRAF inhibitor resistance to melanoma cells through 
      YAP/TAZ activation.
PG  - 462-78
LID - 10.15252/embj.201592081 [doi]
AB  - The activation of transcriptional coactivators YAP and its paralog TAZ has been 
      shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly 
      coupled to actin cytoskeleton architecture. However, the influence of actin 
      remodeling on cancer drug resistance remains largely unexplored. Here, we report 
      a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance 
      in BRAF V600E mutant melanoma cells. Melanoma cells resistant to the BRAF 
      inhibitor PLX4032 exhibit an increase in actin stress fiber formation, which 
      appears to promote the nuclear accumulation of YAP/TAZ. Knockdown of YAP/TAZ 
      reduces the viability of resistant melanoma cells, whereas overexpression of 
      constitutively active YAP induces resistance. Moreover, inhibition of actin 
      polymerization and actomyosin tension in melanoma cells suppresses both YAP/TAZ 
      activation and PLX4032 resistance. Our siRNA library screening identifies actin 
      dynamics regulator TESK1 as a novel vulnerable point of the YAP/TAZ-dependent 
      resistance pathway. These results suggest that inhibition of actin remodeling is 
      a potential strategy to suppress resistance in BRAF inhibitor therapies.
CI  - (c) 2015 The Authors.
FAU - Kim, Min Hwan
AU  - Kim MH
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
FAU - Kim, Jongshin
AU  - Kim J
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
FAU - Hong, Hyowon
AU  - Hong H
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
FAU - Lee, Si-Hyung
AU  - Lee SH
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
FAU - Lee, June-Koo
AU  - Lee JK
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
FAU - Jung, Eunji
AU  - Jung E
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
FAU - Kim, Joon
AU  - Kim J
AD  - Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea 
      joonkim@kaist.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151214
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Actins)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Indoles)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
RN  - 0 (WWTR1 protein, human)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - 207SMY3FQT (Vemurafenib)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
CIN - EMBO J. 2016 Mar 1;35(5):459-61. PMID: 26711176
MH  - Actin Cytoskeleton/drug effects
MH  - Actins
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Shape/drug effects
MH  - Cell Survival/drug effects
MH  - *Drug Resistance, Neoplasm
MH  - Gene Expression Profiling
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Melanoma/genetics/*metabolism
MH  - Mutation
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphoproteins/genetics/*metabolism
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics
MH  - RNA/genetics
MH  - Sulfonamides/*pharmacology
MH  - Trans-Activators
MH  - Transcription Factors
MH  - Transcriptional Coactivator with PDZ-Binding Motif Proteins
MH  - Vemurafenib
MH  - YAP-Signaling Proteins
PMC - PMC4772854
OTO - NOTNLM
OT  - BRAF inhibitor resistance
OT  - TAZ
OT  - YAP
OT  - actin cytoskeleton
OT  - melanoma
EDAT- 2015/12/17 06:00
MHDA- 2016/07/19 06:00
PMCR- 2017/03/01
CRDT- 2015/12/16 06:00
PHST- 2015/05/18 00:00 [received]
PHST- 2015/09/11 00:00 [accepted]
PHST- 2017/03/01 00:00 [pmc-release]
PHST- 2015/12/16 06:00 [entrez]
PHST- 2015/12/17 06:00 [pubmed]
PHST- 2016/07/19 06:00 [medline]
AID - embj.201592081 [pii]
AID - EMBJ201592081 [pii]
AID - 10.15252/embj.201592081 [doi]
PST - ppublish
SO  - EMBO J. 2016 Mar 1;35(5):462-78. doi: 10.15252/embj.201592081. Epub 2015 Dec 14.