dMyc transforms cells into super-competitors

被引:479
作者
Moreno, E [1 ]
Basler, K [1 ]
机构
[1] Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland
关键词
D O I
10.1016/S0092-8674(04)00262-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Overexpression of myc protooncogenes has been implicated in the genesis of many human tumors. Myc proteins seem to regulate diverse biological processes, but their role in tumorigenesis remains enigmatic. Here we use Drosophila imaginal discs to mimic situations in which cells with unequal levels of Myc protein are apposed and show that this invariably elicits a win/lose situation reminiscent of cell competition; cells with lower levels of dMyc are eliminated by apoptosis whereas cells with higher levels of dMyc over-proliferate. We find that this competitive behavior correlates with, and can be corrected by, the activation of the BMP/Dpp survival signaling pathway. Hence the heritable increase in dMyc levels causes cells to behave as "super-competitors" and reveals a novel mode of clonal expansion that causes, but also relies on, the killing of surrounding cells.
引用
收藏
页码:117 / 129
页数:13
相关论文
共 62 条
[1]   Competition and compensation: Coupled to death in development and cancer [J].
Abrams, JM .
CELL, 2002, 110 (04) :403-406
[2]   Morphogenetic apoptosis: A mechanism for correcting discontinuities in morphogen gradients [J].
Adachi-Yamada, T ;
O'Connor, MB .
DEVELOPMENTAL BIOLOGY, 2002, 251 (01) :74-90
[3]   Gene encoding protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer [J].
Anand, N ;
Murthy, S ;
Amann, G ;
Wernick, M ;
Porter, LA ;
Cukier, IH ;
Collins, C ;
Gray, JW ;
Diebold, J ;
Demetrick, DJ ;
Lee, JM .
NATURE GENETICS, 2002, 31 (03) :301-305
[4]   The EGF receptor defines domains of cell cycle progression and survival to regulate cell number in the developing Drosophila eye [J].
Baker, NE ;
Yu, SY .
CELL, 2001, 104 (05) :699-708
[5]   Metastasis genes: A progression puzzle [J].
Bernards, R ;
Weinberg, RA .
NATURE, 2002, 418 (6900) :823-823
[6]   Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4 [J].
Böhni, R ;
Riesgo-Escovar, J ;
Oldham, S ;
Brogiolo, W ;
Stocker, H ;
Andruss, BF ;
Beckingham, K ;
Hafen, E .
CELL, 1999, 97 (07) :865-875
[7]   N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis [J].
Boon, K ;
Caron, HN ;
van Asperen, R ;
Valentijn, L ;
Hermus, MC ;
van Sluis, P ;
Roobeek, I ;
Weis, I ;
Voûte, PA ;
Schwab, M ;
Versteeg, R .
EMBO JOURNAL, 2001, 20 (06) :1383-1393
[8]   A P-insertion screen identifying novel X-linked essential genes in Drosophila [J].
Bourbon, HM ;
Gonzy-Treboul, G ;
Peronnet, F ;
Alin, MF ;
Ardourel, C ;
Benassayag, C ;
Cribbs, D ;
Deutsch, J ;
Ferrer, P ;
Haenlin, M ;
Lepesant, JA ;
Noselli, S ;
Vincent, A .
MECHANISMS OF DEVELOPMENT, 2002, 110 (1-2) :71-83
[9]  
Braakhuis BJM, 2003, CANCER RES, V63, P1727
[10]   THE SMALL GTPASE RAB5 FUNCTIONS AS A REGULATORY FACTOR IN THE EARLY ENDOCYTIC PATHWAY [J].
BUCCI, C ;
PARTON, RG ;
MATHER, IH ;
STUNNENBERG, H ;
SIMONS, K ;
HOFLACK, B ;
ZERIAL, M .
CELL, 1992, 70 (05) :715-728