PMID- 21245096
OWN - NLM
STAT- MEDLINE
DCOM- 20110502
LR  - 20220321
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 71
IP  - 3
DP  - 2011 Feb 1
TI  - LATS2 is a tumor suppressor gene of malignant mesothelioma.
PG  - 873-83
LID - 10.1158/0008-5472.CAN-10-2164 [doi]
AB  - Malignant mesothelioma (MM) is an aggressive neoplasm associated with asbestos 
      exposure. We carried out genome-wide array-based comparative genomic 
      hybridization analysis with 14 MM cell lines. Three cell lines showed overlapping 
      homozygous deletion at chromosome 13q12, which harbored the LATS2 (large tumor 
      suppressor homolog 2) gene. With 6 other MM cell lines and 25 MM tumors, we found 
      10 inactivating homozygous deletions or mutations of LATS2 among 45 MMs. LATS2 
      encodes a serine/threonine kinase, a component of the Hippo tumor-suppressive 
      signaling pathway, and we transduced LATS2 in MM cells with its mutation. 
      Transduction of LATS2 inactivated oncoprotein YAP, a transcriptional coactivator, 
      via phosphorylation, and inhibited MM cell growth. We also analyzed LATS2 
      immunohistochemically and found that 13 of 45 MM tumors had low expression of 
      LATS2. Because NF2 is genetically mutated in 40% to 50% of MM, our data indicate 
      that Hippo pathway dysregulation is frequent in MM cells with inactivation of 
      LATS2 or an upstream regulator of this pathway, Merlin, which is encoded by NF2. 
      Thus, our results suggest that the inactivation of LATS2 is one of the key 
      mechanisms for constitutive activation of YAP, which induces deregulation of MM 
      cell proliferation.
FAU - Murakami, Hideki
AU  - Murakami H
AD  - Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, 
      Japan.
FAU - Mizuno, Tetsuya
AU  - Mizuno T
FAU - Taniguchi, Tetsuo
AU  - Taniguchi T
FAU - Fujii, Makiko
AU  - Fujii M
FAU - Ishiguro, Futoshi
AU  - Ishiguro F
FAU - Fukui, Takayuki
AU  - Fukui T
FAU - Akatsuka, Shinya
AU  - Akatsuka S
FAU - Horio, Yoshitsugu
AU  - Horio Y
FAU - Hida, Toyoaki
AU  - Hida T
FAU - Kondo, Yutaka
AU  - Kondo Y
FAU - Toyokuni, Shinya
AU  - Toyokuni S
FAU - Osada, Hirotaka
AU  - Osada H
FAU - Sekido, Yoshitaka
AU  - Sekido Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110118
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Neurofibromin 2)
RN  - 0 (SAV1 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.1.11 (LATS2 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Cell Cycle Proteins/genetics
MH  - Cell Growth Processes/genetics
MH  - Cell Line, Tumor
MH  - Chromosomes, Human, Pair 13
MH  - Comparative Genomic Hybridization
MH  - *Gene Deletion
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Immunohistochemistry
MH  - Mesothelioma/*genetics/pathology
MH  - Neurofibromin 2/genetics
MH  - Protein Serine-Threonine Kinases/*genetics
MH  - Transduction, Genetic
MH  - Tumor Suppressor Proteins/*genetics
EDAT- 2011/01/20 06:00
MHDA- 2011/05/03 06:00
CRDT- 2011/01/20 06:00
PHST- 2011/01/20 06:00 [entrez]
PHST- 2011/01/20 06:00 [pubmed]
PHST- 2011/05/03 06:00 [medline]
AID - 0008-5472.CAN-10-2164 [pii]
AID - 10.1158/0008-5472.CAN-10-2164 [doi]
PST - ppublish
SO  - Cancer Res. 2011 Feb 1;71(3):873-83. doi: 10.1158/0008-5472.CAN-10-2164. Epub 
      2011 Jan 18.