| | |  | | | | Record from Web of Science® | | | | | | |
| Autophagy suppresses tumor progression by limiting chromosomal instability |
|
|
| Author(s): Mathew R (Mathew, Robin), Kongara S (Kongara, Sameera), Beaudoin B (Beaudoin, Brian), Karp CM (Karp, Cristina M.), Bray K (Bray, Kevin), Degenhardt K (Degenhardt, Kurt), Chen GH (Chen, Guanghua), Jin SK (Jin, Shengkan), White E (White, Eileen) |
| Source: GENES & DEVELOPMENT Volume: 21 Issue: 11 Pages: 1367-1381 Published: JUN 1 2007 |
| Times Cited: 91 References: 45 |
| Abstract: Autophagy is a bulk degradation process that promotes survival under metabolic stress, but it can also be a means of cell death if executed to completion. Monoallelic loss of the essential autophagy gene beclin1 causes susceptibility to metabolic stress, but also promotes tumorigenesis. This raises the paradox that the loss of a survival pathway enhances tumor growth, where the exact mechanism is not known. Here, we show that compromised autophagy promoted chromosome instability. Failure to sustain metabolism through autophagy was associated with increased DNA damage, gene amplification, and aneuploidy, and this genomic instability may promote tumorigenesis. Thus, autophagy maintains metabolism and survival during metabolic stress that serves to protect the genome, providing an explanation for how the loss of a survival pathway leads to tumor progression. Identification of this novel role of autophagy may be important for rational chemotherapy and therapeutic exploitation of autophagy inducers as potential chemopreventive agents. |
| Document Type: Article |
| Language: English |
| Reprint Address: White, E (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA |
Addresses:
1. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA
2. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
3. Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA
4. Univ Med & Dent New Jersey, Dept Pharmacol, Piscataway, NJ 08854 USA
5. Canc Inst New Jersey, New Brunswick, NJ 08903 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: 174NH |
| ISSN: 0890-9369 |
| DOI: 10.1101/gad.1545107 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |