Signal-dependent control of autophagy-related gene expression.
Several tumors arise from deregulated signaling pathways leading to increased proliferation and impairment of differentiation. To bypass endogenous control mechanisms and to survive the environmental stress associated with increased growth, tumor cells acquire a plethora of modifications that ultimately tend to down-regulate the ability to undergo apoptosis and exacerbate prosurvival mechanisms. Autophagy is an evolutionarily conserved mechanism through which cells recycle essential molecular constituents or eliminate damaged organelles under stress conditions imposed by nutrients or growth factors deprivation. As such, autophagy acts as a prosurvival mechanism for cancer cells. However, when overactivated, autophagy could also represent a cell death mechanism acting through self-cannibalization. Therefore, understanding the various signaling pathways that regulate autophagy could be of extreme importance. Indeed, the identification of specific molecular targets amenable to pharmacological manipulation to induce cancer cell self-cannibalization could represent a promising approach to treat apoptosis-resistant tumors.
Chiacchiera
Fulvio
F
Laboratory of Signal-Dependent Transcription, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Simone
Cristiano
C
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured