Showing papers by "Mojgan Djavaheri-Mergny published in 2007"

Regulation of autophagy by NFkappaB transcription factor and reactives oxygen species.

Abstract: The NF-kappaB transcription factor is an important anti-apoptotic factor, which is frequently deregulated in cancer cells. We have recently demonstrated that NF-kappaB activation mediates the repression of autophagy in response to TNFa in three models of cancer cell lines. In contrast, in the absence of NF-kappaB activation, TNFa induces macroautophagy (autophagy), which requires reactive oxygen species (ROS) production and participates in the TNFalpha-induced apoptotic signaling pathway. Autophagy-dependent apoptosis was also observed following direct addition of ROS to cells. Moreover, addition of rapamycin to TNFalpha renders these cells susceptible to the cytotoxic effect of this cytokine. These findings highlight the regulation of autophagy by oxidative stress and support the idea that repression of autophagy by NF-kappaB may constitute a novel anti-apoptotic function of this transcription factor. We also bring evidence that direct stimulation of autophagy may represent a new therapeutic strategy for overcoming the NF-kappaB-dependent chemoresistance of cancer cells.

Autophagy and Autophagic Cell Death

Abstract: Macroautophagy or autophagy is a degradative pathway terminating in the lysosomal compartment after the formation of a cytoplasmic vacuole that engulfs macromolecules and organelles. During the last decade, progress made in our understanding of the molecular controls of autophagy has uncovered the importance of tumor suppressor molecules in the stimulation of autophagy. Downexpression of autophagy is an early event during tumorigenesis. However, the relation between autophagy and tumor progression seems to be more complex because cancer cells are able to trigger autophagy in response to various situations including changes in their extracellular environment and cancer treatments. The role of autophagy in cancer cells balances between two apparently opposite outcomes. Autophagy as a stress response mechanism can protect cancer cells from various insults. But autophagy can eliminate cancer cells by triggering autophagic cell death. These two aspects of autophagy will be discussed in this review.