Yes-associated protein (YAP) functions as a tumor suppressor in breast.
Yes-associated protein (YAP) has been shown to positively regulate p53 family members and to be negatively regulated by the AKT proto-oncogene product in promoting apoptosis. On the basis of this function and its location at 11q22.2, a site of frequent loss of heterozygosity (LOH) in breast cancer, we investigated whether YAP is a tumor suppressor in breast. Examination of tumors by immunohistochemistry demonstrated significant loss of YAP protein. LOH analysis revealed that protein loss correlates with specific deletion of the YAP gene locus. Functionally, short hairpin RNA knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, inhibited the response to taxol and enhanced tumor growth in nude mice. This is the first report indicating YAP as a tumor suppressor, revealing its decreased expression in breast cancer as well as demonstrating the functional implications of YAP loss in several aspects of cancer signaling.
Yuan
M
M
Cell Survival Signalling Laboratory, Centre for Molecular Oncology, Institute of Cancer, Charterhouse Square, London, UK.
Tomlinson
V
V
Lara
R
R
Holliday
D
D
Chelala
C
C
Harada
T
T
Gangeswaran
R
R
Manson-Bishop
C
C
Smith
P
P
Danovi
S A
SA
Pardo
O
O
Crook
T
T
Mein
C A
CA
Lemoine
N R
NR
Jones
L J
LJ
Basu
S
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D023102:Anoikis / Q000187:drug effects; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004351:Drug Resistance / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; C000715470:MAS1 protein, human; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017239:Paclitaxel