RRC ID |
35957
|
著者 |
Clemente-Ruiz M, Murillo-Maldonado JM, Benhra N, Barrio L, Pérez L, Quiroga G, Nebreda AR, Milán M.
|
タイトル |
Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.
|
ジャーナル |
Dev Cell
|
Abstract |
Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis.
|
巻・号 |
36(3)
|
ページ |
290-302
|
公開日 |
2016-2-8
|
DOI |
10.1016/j.devcel.2016.01.008
|
PII |
S1534-5807(16)00042-3
|
PMID |
26859353
|
MeSH |
Aneuploidy
Animals
Apoptosis / genetics
Cell Transformation, Neoplastic / genetics*
Chromosomal Instability / genetics*
DNA Repair / genetics
Drosophila melanogaster
Gene Dosage / genetics
Reactive Oxygen Species / metabolism
|
IF |
10.092
|
引用数 |
22
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ショウジョウバエ |
7393R-3
3749R-2 |