Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model
AUTOR(ES)
Uhlirova, Mirka
FONTE
National Academy of Sciences
RESUMO
The role of c-Jun N-terminal kinase (JNK) signaling in cancer is enigmatic, and both tumor-promoting and tumor-suppressing functions have been ascribed to JNK pathway components. We have used the Drosophila eye to investigate the function of the JNK pathway in three different tumor models of increasing malignancy. Benign lesions caused by loss of the neoplastic tumor suppressor gene scribble can efficiently be eliminated by JNK-induced apoptosis. In such a scenario, the eye reverts to a wild-type phenotype, indicating that the JNK pathway prevents tumor formation. The situation changes in the case of aggressive tissue overgrowth, which can be induced by oncogenic activation of the Ras/Raf pathway in the eye, or in malignant invasive tumors resulting when Raf activation is combined with loss of scribble. The growth of these more aggressive tumor types is significantly, yet incompletely, suppressed by JNK-mediated apoptosis. Remarkably, oncogenic Raf and JNK cooperate in these tumors, to induce massive hyperplasia in adjacent wild-type tissue. Thus, depending on the genetic context, JNK signaling can eradicate tumors by removing premalignant cells, or promote aberrant overgrowth in tissues surrounding primary lesions.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1201591Documentos Relacionados
- Impairment of ubiquitylation by mutation in Drosophila E1 promotes both cell-autonomous and non-cell-autonomous Ras-ERK activation in vivo
- Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system
- Srf–/– ES cells display non-cell-autonomous impairment in mesodermal differentiation
- A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner
- Plasmodesmal-Associated Protein Kinase in Tobacco and Arabidopsis Recognizes a Subset of Non-Cell-Autonomous ProteinsW⃞