PMID- 24648515
OWN - NLM
STAT- MEDLINE
DCOM- 20140627
LR  - 20220330
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 289
IP  - 19
DP  - 2014 May 9
TI  - The transcriptional regulators TAZ and YAP direct transforming growth factor 
      beta-induced tumorigenic phenotypes in breast cancer cells.
PG  - 13461-74
LID - 10.1074/jbc.M113.529115 [doi]
AB  - Uncontrolled transforming growth factor-beta (TGFbeta) signaling promotes aggressive 
      metastatic properties in late-stage breast cancers. However, how TGFbeta-mediated 
      cues are directed to induce tumorigenic events is poorly understood, particularly 
      given that TGFbeta has clear tumor suppressing activity in other contexts. Here, we 
      demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key 
      effectors of the Hippo pathway, are necessary to promote and maintain 
      TGFbeta-induced tumorigenic phenotypes in breast cancer cells. Interactions between 
      TAZ/YAP, TGFbeta-activated SMAD2/3, and TEAD transcription factors reveal convergent 
      roles for these factors in the nucleus. Genome-wide expression analyses indicate 
      that TAZ/YAP, TEADs, and TGFbeta-induced signals coordinate a specific 
      pro-tumorigenic transcriptional program. Importantly, genes cooperatively 
      regulated by TAZ/YAP, TEAD, and TGFbeta, such as the novel targets NEGR1 and UCA1, 
      are necessary for maintaining tumorigenic activity in metastatic breast cancer 
      cells. Nuclear TAZ/YAP also cooperate with TGFbeta signaling to promote phenotypic 
      and transcriptional changes in nontumorigenic cells to overcome TGFbeta-repressive 
      effects. Our work thus identifies cross-talk between nuclear TAZ/YAP and TGFbeta 
      signaling in breast cancer cells, revealing novel insight into late-stage 
      disease-driving mechanisms.
FAU - Hiemer, Samantha E
AU  - Hiemer SE
AD  - From the Department of Biochemistry, Boston University School of Medicine, 
      Boston, Massachusetts 02118.
FAU - Szymaniak, Aleksander D
AU  - Szymaniak AD
FAU - Varelas, Xaralabos
AU  - Varelas X
LA  - eng
GR  - UL1 TR000157/TR/NCATS NIH HHS/United States
GR  - UL1-TR000157/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140319
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cell Adhesion Molecules, Neuronal)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (NEGR1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (UCA1 RNA, human)
RN  - 0 (YY1AP1 protein, human)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (TAFAZZIN protein, human)
SB  - IM
MH  - Acyltransferases
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Cell Adhesion Molecules, Neuronal
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Female
MH  - GPI-Linked Proteins
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Nuclear Proteins/genetics/*metabolism
MH  - RNA, Long Noncoding/genetics/metabolism
MH  - RNA, Neoplasm/genetics/metabolism
MH  - *Signal Transduction
MH  - Smad2 Protein/genetics/metabolism
MH  - Smad3 Protein/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transforming Growth Factor beta/genetics/*metabolism
PMC - PMC4036353
OTO - NOTNLM
OT  - Breast Cancer
OT  - Cell Migration
OT  - Cell Signaling
OT  - Coregulator Transcription
OT  - Hippo Pathway
OT  - Signal Transduction
OT  - Signaling Cross-talk
OT  - Transforming Growth Factor beta (TGFbeta)
OT  - YAP/TAZ
EDAT- 2014/03/22 06:00
MHDA- 2014/06/28 06:00
PMCR- 2015/05/09
CRDT- 2014/03/21 06:00
PHST- 2014/03/21 06:00 [entrez]
PHST- 2014/03/22 06:00 [pubmed]
PHST- 2014/06/28 06:00 [medline]
PHST- 2015/05/09 00:00 [pmc-release]
AID - S0021-9258(20)38825-6 [pii]
AID - M113.529115 [pii]
AID - 10.1074/jbc.M113.529115 [doi]
PST - ppublish
SO  - J Biol Chem. 2014 May 9;289(19):13461-74. doi: 10.1074/jbc.M113.529115. Epub 2014 
      Mar 19.