PMID- 21610251
OWN - NLM
STAT- MEDLINE
DCOM- 20110920
LR  - 20211203
IS  - 1937-9145 (Electronic)
IS  - 1937-9145 (Print)
IS  - 1945-0877 (Linking)
VI  - 4
IP  - 174
DP  - 2011 May 24
TI  - alpha-catenin is a tumor suppressor that controls cell accumulation by regulating the 
      localization and activity of the transcriptional coactivator Yap1.
PG  - ra33
LID - 10.1126/scisignal.2001823 [doi]
AB  - The Hippo pathway regulates contact inhibition of cell proliferation and, 
      ultimately, organ size in diverse multicellular organisms. Inactivation of the 
      Hippo pathway promotes nuclear localization of the transcriptional coactivator 
      Yap1, a Hippo pathway effector, and can cause cancer. Here, we show that deletion 
      of alphaE (alpha epithelial) catenin in the hair follicle stem cell compartment resulted 
      in the development of skin squamous cell carcinoma in mice. Tumor formation was 
      accelerated by simultaneous deletion of alphaE-catenin and the tumor 
      suppressor-encoding gene p53. A small interfering RNA screen revealed a 
      functional connection between alphaE-catenin and Yap1. By interacting with Yap1, 
      alphaE-catenin promoted its cytoplasmic localization, and Yap1 showed constitutive 
      nuclear localization in alphaE-catenin-null cells. We also found an inverse 
      correlation between alphaE-catenin abundance and Yap1 activation in human squamous 
      cell carcinoma tumors. These findings identify alphaE-catenin as a tumor suppressor 
      that inhibits Yap1 activity and sequesters it in the cytoplasm.
FAU - Silvis, Mark R
AU  - Silvis MR
AD  - Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 
      98109, USA.
FAU - Kreger, Bridget T
AU  - Kreger BT
FAU - Lien, Wen-Hui
AU  - Lien WH
FAU - Klezovitch, Olga
AU  - Klezovitch O
FAU - Rudakova, G Marianna
AU  - Rudakova GM
FAU - Camargo, Fernando D
AU  - Camargo FD
FAU - Lantz, Dan M
AU  - Lantz DM
FAU - Seykora, John T
AU  - Seykora JT
FAU - Vasioukhin, Valeri
AU  - Vasioukhin V
LA  - eng
GR  - R01 AR051380/AR/NIAMS NIH HHS/United States
GR  - R01 CA098161/CA/NCI NIH HHS/United States
GR  - R01 CA131047/CA/NCI NIH HHS/United States
GR  - T32 CA009657/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20110524
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - 0 (Yap1 protein, mouse)
RN  - 0 (alpha Catenin)
SB  - IM
MH  - Active Transport, Cell Nucleus/genetics
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - Carcinoma, Squamous Cell/genetics/*metabolism/pathology
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Cell Nucleus/genetics/*metabolism
MH  - Cell Proliferation
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Mice, Transgenic
MH  - Phosphoproteins/genetics/*metabolism
MH  - Transcription Factors
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
MH  - YAP-Signaling Proteins
MH  - alpha Catenin/genetics/*metabolism
PMC - PMC3366274
MID - NIHMS376579
EDAT- 2011/05/26 06:00
MHDA- 2011/09/21 06:00
PMCR- 2012/06/03
CRDT- 2011/05/26 06:00
PHST- 2011/05/26 06:00 [entrez]
PHST- 2011/05/26 06:00 [pubmed]
PHST- 2011/09/21 06:00 [medline]
PHST- 2012/06/03 00:00 [pmc-release]
AID - 4/174/ra33 [pii]
AID - 10.1126/scisignal.2001823 [doi]
PST - epublish
SO  - Sci Signal. 2011 May 24;4(174):ra33. doi: 10.1126/scisignal.2001823.