| Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas. | |
| | |
MedLine Citation:
|
PMID: 20388797 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Apoptosis and senescence are cellular failsafe programs that counteract excessive mitogenic signaling observed in cancer cells. Melanoma is known for its notorious resistance to apoptotic processes; therefore, senescence, which remains poorly understood in melanomas, can be viewed as a therapeutic alternative. Microphthalmia-associated transcription factor (MITF), in which its M transcript is specifically expressed in melanocyte cells, plays a critical role in melanoma proliferation, and its specific inhibition is associated with G(0)-G(1) growth arrest. Interestingly, decreased MITF expression has been described in senescent melanocytes, and we have observed an inhibition of MITF expression in melanoma cells exposed to chemotherapeutic drugs that induce their senescence. All these observations thereby question the role of MITF in controlling senescence in melanoma cells. Here, we report that long-term depletion of MITF in melanoma cells triggers a senescence program characterized by typical morphologic and biochemical changes associated with a sustained growth arrest. Further, we show that MITF-silenced cells engage a DNA damage response (DDR) signaling pathway, leading to p53 upregulation, which is critically required for senescence entry. This study uncovers the existence of a lineage-restricted DDR/p53 signaling pathway that is inhibited by MITF to prevent senescence and favor melanoma cell proliferation. |
| | |
Authors:
|
Sandy Giuliano; Yann Cheli; Micka?l Ohanna; Caroline Bonet; Laurent Beuret; Karine Bille; Agn?s Loubat; V?ronique Hofman; Paul Hofman; Gilles Ponzio; Philippe Bahadoran; Robert Ballotti; Corine Bertolotto |
Related Documents
:
|
7829227 - Growth properties of a human melanoma cell line are altered by adeno-associated parvovi... 3796057 - Hydrocortisone is associated with cell surface blebbing in cultures of human embryonic ... 17658517 - Inhibitory role of rhoa on senescence-like growth arrest by a mechanism involving modul... 12429237 - Transplantation of m213-2o cells with enhanced gad67 expression into the inferior colli... 20455727 - Hmg-coa reductase inhibitor lovastatin causes reversible cytoskeleton perturbation by r... 19454697 - Cd45-mediated fodrin cleavage during galectin-1 t cell death promotes phagocytic cleara... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-13 |
Journal Detail:
|
Title: Cancer research Volume: 70 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2010 May |
Date Detail:
|
Created Date: 2010-04-30 Completed Date: 2010-05-27 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
|
Languages: eng Pagination: 3813-22 Citation Subset: IM |
Copyright Information:
|
(c)2010 AACR. |
Affiliation:
|
Institut National de la Sante et de la Recherche Medicale U895, University of Nice Sophia-Antipolis, Nice, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Aging / physiology Cell Line, Tumor Cell Lineage / physiology DNA Damage* Humans Melanoma / genetics*, metabolism, pathology Melanoma, Experimental / genetics, metabolism, pathology Mice Microphthalmia-Associated Transcription Factor / deficiency*, genetics, metabolism Mitosis / genetics Signal Transduction Tumor Suppressor Protein p53 / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Microphthalmia-Associated Transcription Factor; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Molecular mechanism of chemoresistance by astrocyte elevated gene-1.
Next Document: Xg Expression in Ewing's Sarcoma Is of Prognostic Value and Contributes to Tumor Invasiveness.