PMID- 21397843
OWN - NLM
STAT- MEDLINE
DCOM- 20110512
LR  - 20190614
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Linking)
VI  - 20
IP  - 3
DP  - 2011 Mar 15
TI  - Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila.
PG  - 315-28
LID - 10.1016/j.devcel.2011.02.007 [doi]
AB  - A newly emerged oncogenic cell in the epithelial population has to confront 
      antitumor selective pressures in the host tissue. However, the mechanisms by 
      which surrounding normal tissue exerts antitumor effects against oncogenically 
      transformed cells are poorly understood. In Drosophila imaginal epithelia, clones 
      of cells mutant for evolutionarily conserved tumor suppressor genes such as scrib 
      or dlg lose their epithelial integrity and are eliminated from epithelia when 
      surrounded by wild-type tissue. Here, we show that surrounding normal cells 
      activate nonapoptotic JNK signaling in response to the emergence of oncogenic 
      mutant cells. This JNK activation leads to upregulation of PVR, the Drosophila 
      PDGF/VEGF receptor. Genetic and time-lapse imaging analyses reveal that PVR 
      expression in surrounding cells activates the ELMO/Mbc-mediated phagocytic 
      pathway, thereby eliminating oncogenic neighbors by engulfment. Our data indicate 
      that JNK-mediated cell engulfment could be an evolutionarily conserved intrinsic 
      tumor-suppression mechanism that eliminates premalignant cells from epithelia.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Ohsawa, Shizue
AU  - Ohsawa S
AD  - Department of Cell Biology, G-COE, Kobe University Graduate School of Medicine, 
      7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Sugimura, Kaoru
AU  - Sugimura K
FAU - Takino, Kyoko
AU  - Takino K
FAU - Xu, Tian
AU  - Xu T
FAU - Miyawaki, Atsushi
AU  - Miyawaki A
FAU - Igaki, Tatsushi
AU  - Igaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Ced-12 protein, Drosophila)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Scrib protein, Drosophila)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (egr protein, Drosophila)
RN  - EC 2.7.10.1 (Pvr protein, Drosophila)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
CIN - Nat Rev Cancer. 2011 May;11(5):314. PMID: 21508967
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Animals
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster/*anatomy & histology/*embryology/metabolism
MH  - Enzyme Activation
MH  - Epithelium/embryology/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Neoplasms/pathology/physiopathology
MH  - *Oncogenes
MH  - Phagocytosis/*physiology
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Signal Transduction/physiology
MH  - Tumor Suppressor Proteins/genetics/metabolism
EDAT- 2011/03/15 06:00
MHDA- 2011/05/13 06:00
CRDT- 2011/03/15 06:00
PHST- 2010/07/23 00:00 [received]
PHST- 2011/01/21 00:00 [revised]
PHST- 2011/02/18 00:00 [accepted]
PHST- 2011/03/15 06:00 [entrez]
PHST- 2011/03/15 06:00 [pubmed]
PHST- 2011/05/13 06:00 [medline]
AID - S1534-5807(11)00076-1 [pii]
AID - 10.1016/j.devcel.2011.02.007 [doi]
PST - ppublish
SO  - Dev Cell. 2011 Mar 15;20(3):315-28. doi: 10.1016/j.devcel.2011.02.007.