| RRC ID |
21902
|
| 著者 |
Ohsawa S, Sato Y, Enomoto M, Nakamura M, Betsumiya A, Igaki T.
|
| タイトル |
Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila.
|
| ジャーナル |
Nature
|
| Abstract |
Mitochondrial respiratory function is frequently impaired in human cancers. However, the mechanisms by which mitochondrial dysfunction contributes to tumour progression remain elusive. Here we show in Drosophila imaginal epithelium that defects in mitochondrial function potently induce tumour progression of surrounding tissue in conjunction with oncogenic Ras. Our data show that Ras activation and mitochondrial dysfunction cooperatively stimulate production of reactive oxygen species, which causes activation of c-Jun amino (N)-terminal kinase (JNK) signalling. JNK cooperates with oncogenic Ras to inactivate the Hippo pathway, leading to upregulation of its targets Unpaired (an interleukin-6 homologue) and Wingless (a Wnt homologue). Mitochondrial dysfunction in Ras-activated cells further cooperates with Ras signalling in neighbouring cells with normal mitochondrial function, causing benign tumours to exhibit metastatic behaviour. Our findings provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras.
|
| 巻・号 |
490(7421)
|
| ページ |
547-51
|
| 公開日 |
2012-10-25
|
| DOI |
10.1038/nature11452
|
| PII |
nature11452
|
| PMID |
23023132
|
| MeSH |
Animals
Cell Transformation, Neoplastic
Clone Cells / metabolism
Clone Cells / pathology
Compound Eye, Arthropod / growth & development
Compound Eye, Arthropod / pathology
Compound Eye, Arthropod / ultrastructure
Disease Models, Animal
Disease Progression*
Drosophila Proteins / metabolism*
Drosophila melanogaster / cytology*
Drosophila melanogaster / enzymology
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism*
Imaginal Discs / metabolism
Imaginal Discs / pathology
Intracellular Signaling Peptides and Proteins / metabolism*
JNK Mitogen-Activated Protein Kinases / metabolism
Mitochondria / metabolism
Mitochondria / pathology*
Neoplasms / metabolism
Neoplasms / pathology*
Oncogene Protein p21(ras) / genetics
Oncogene Protein p21(ras) / metabolism
Oxidative Stress
Protein Serine-Threonine Kinases / metabolism*
Reactive Oxygen Species / metabolism
Signal Transduction*
Transcription Factors / metabolism
Up-Regulation
Wnt1 Protein / metabolism
|
| IF |
42.779
|
| 引用数 |
119
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
5993R-1
5993R-2
4889R-3
4889R-4
pdswk10101
CG9140KG01287
CG11455d08265
RFeSPk11704
mRpL4k16084
mRpL13/CG10602f0419
mRpL24f6692
mRpL17KG06809
Df(1)BSC352 and osupd-4 |
