IGF1 Promotes Resistance to Apoptosis in Melanoma Cells through an Increased Expression of BCL2, BCL-X(L), and Survivin
- Type de publi. : Article dans une revue
- Date de publi. : 01/06/2008
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Auteurs :
Caroline HilmiLionel LarribèreSandy GiulianoKarine BilleJean-Paul OrtonneRobert BallottiCorine Bertolotto
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Organismes :
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
Service de Dermatologie [Nice]
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes
- Publié dans Journal of Investigative Dermatology le 24/10/2020
Résumé : IGF1 plays a key role in the development and growth of multiple tumors and in the prevention of apoptosis. In melanoma cells, IGF1 has been shown to mediate resistance to anoikis-induced apoptosis. However, the effect of IGF1 on other proapoptotic stimuli has never been reported. Further, the molecular mechanisms by which IGF1 mediates its prosurvival properties in melanoma cells remain unknown. Here, we demonstrate that IGF1 impairs the onset of tumor necrosis factor-related apoptosis-inducing ligand and staurosporine-induced apoptosis in melanoma cells expressing either wild-type or oncogenic B-Raf. Further, we show that IGF1 inhibits mitochondrial damage that occurs during apoptosis, thereby indicating that IGF1 acts at the level of mitochondria to mediate its antiapoptotic stimuli. Accordingly, IGF1 increases the mRNA levels and protein expression of antiapoptotic members of the BCL2 family--BCL2 and BCL-X(L)--and that of the inhibitor of apoptosis protein, survivin. Further, their specific silencing by small interfering RNA prevents the protective effect of IGF1. These findings therefore delineate the molecular mechanisms by which IGF1 mediates its prosurvival properties and provide a basis for clinical strategies designed to neutralize IGF1 or its target genes.
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