Reference - Detail
| RRC ID | 35957 |
|---|---|
| Author | Clemente-Ruiz M, Murillo-Maldonado JM, Benhra N, Barrio L, Pérez L, Quiroga G, Nebreda AR, Milán M. |
| Title | Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis. |
| Journal | 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. |
| Volume | 36(3) |
| Pages | 290-302 |
| Published | 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 |
| Times Cited | 22 |
| WOS Category | DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 39 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | 7393R-3 3749R-2 |