TITLE:
Autophagic cell death: A new frontier in cancer research
AUTHORS:
S. Zappavigna, A. Luce, G. Vitale, N. Merola, S. Facchini, M. Caraglia
KEYWORDS:
Autophagy; Cancer; Cellular Death; mTOR; PPAR-γ
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.2,
February
28,
2013
ABSTRACT:
Autophagy is a conserved and tightly regulated cellular catabolic process that involves the lysosomal degradation pathway.
Intracellular recycling of macromolecules and organelles provided by
autophagy is an integral part of normal cellular function and permits cells
survival under starvation conditions, maintaining cell growth and the
homeostasis of organisms. In addition to its normal role in cell physiology,
auto- phagy is closely linked to both tumorigenesis and cancer cell response to
treatments. In fact, anticancer drugs can induce autophagy but it remains contro-
versial whether this process leads to cancer cell death or protects cancer
cells from cellular stress. The role of autophagy in cancer is complex and is
likely dependent on tumor type, stage, and genetic context. However, recent
evidences demonstrate a tight interconnection of autophagy with several cell
death pathways and reveal an active contribution of auto- phagy to cell death.
When autophagy is directly in- volved in the death process, the cell death
process is designated “autophagic cell death” (ACD). In this review, we will
give a comprehensive overview of the autophagic signaling pathway, its role and
regulation in cancer cells; moreover, we will try to define the molecular
mechanisms at the basis of the autophagic cell death showing that PPAR-γ activation plays a role in the induction of autophagy in cancer cells.