Sphingolipids as Regulators of Autophagy and Endocytic Trafficking

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Abstract

Macroautophagy (herein referred to as autophagy) is a highly conserved stress response that engulfs damaged proteins, lipids, and/or organelles within double-membrane vesicles called autophagosomes for lysosomal degradation. Dysregulated autophagy is a hallmark of cancer; and thus, there is great interest in modulating autophagy for cancer therapy. Sphingolipids regulate each step of autophagosome biogenesis with roles for sphingolipid metabolites and enzymes spanning from the initial step of de novo ceramide synthesis to the sphingosine-1-phosphate lyase 1–mediated exit from the sphingolipid pathway. Notably, sphingolipid metabolism occurs at several of the organelles that contribute to autophagosome biogenesis to suggest that local changes in sphingolipids may regulate autophagy. As sphingolipid metabolism is frequently dysregulated in cancer, a molecular understanding of sphingolipids in stress-induced autophagy may provide insight into the mechanisms driving tumor development and progression. On the contrary, modulation of sphingolipid metabolites and/or enzymes can induce autophagy-dependent cell death for cancer therapy. This chapter will overview the major steps in mammalian autophagy, discuss the regulation of each step by sphingolipid metabolites, and describe the functions of sphingolipid-mediated autophagy in cancer. While our understanding of the signaling and biophysical properties of sphingolipids in autophagy remains in its infancy, the unique cross talk between the two pathways is an exciting area for further development, particularly in the context of cancer therapy.

Original languageEnglish (US)
Title of host publicationAdvances in Cancer Research
EditorsCharles E. Chalfant, Paul B. Fisher
PublisherAcademic Press Inc.
Pages27-60
Number of pages34
ISBN (Print)9780128142233
DOIs
StatePublished - Jan 1 2018

Publication series

NameAdvances in Cancer Research
Volume140
ISSN (Print)0065-230X
ISSN (Electronic)2162-5557

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Young, M. M., & Wang, H. G. (2018). Sphingolipids as Regulators of Autophagy and Endocytic Trafficking. In C. E. Chalfant, & P. B. Fisher (Eds.), Advances in Cancer Research (pp. 27-60). (Advances in Cancer Research; Vol. 140). Academic Press Inc.. https://doi.org/10.1016/bs.acr.2018.04.008