Functions of autophagy in the tumor microenvironment and cancer metastasis

Macro‐autophagy is an ancient and highly conserved self‐degradative process that plays a homeostatic role in normal cells by eliminating organelles, pathogens, and protein aggregates. Autophagy, as it is routinely referred to, also allows cells to maintain metabolic sufficiency and survive under con...

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Bibliographic Details
Published in:The FEBS journal 2018-05, Vol.285 (10), p.1751-1766
Main Authors: Mowers, Erin E., Sharifi, Marina N., Macleod, Kay F.
Format: Article
Language:English
Subjects:
Amino acids
Autophagy
Autophagy - physiology
Biodegradation
Cancer
Cell adhesion & migration
Cell migration
Dependence
Fatty acids
Growth rate
Humans
invasion
Malignancy
Metabolism
Metastases
metastasis
mitophagy
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasms - pathology
Neoplastic Stem Cells - pathology
Nucleotides
Nutrients
Organelles
Phagocytosis
Proteins
Stem cells
tumor cell migration
Tumor cells
Tumor Microenvironment
tumor stem cells
Tumors
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Summary:Macro‐autophagy is an ancient and highly conserved self‐degradative process that plays a homeostatic role in normal cells by eliminating organelles, pathogens, and protein aggregates. Autophagy, as it is routinely referred to, also allows cells to maintain metabolic sufficiency and survive under conditions of nutrient stress by recycling the by‐products of autophagic degradation, such as fatty acids, amino acids, and nucleotides. Tumor cells are more reliant than normal cells on autophagy for survival in part due to their rapid growth rate, altered metabolism, and nutrient‐deprived growth environment. How this dependence of tumor cells on autophagy affects their progression to malignancy and metastatic disease is an area of increasing research focus. Here, we review recent work identifying critical functions for autophagy in tumor cell migration and invasion, tumor stem cell maintenance and therapy resistance, and cross‐talk between tumor cells and their microenvironment. Autophagy is upregulated as tumors progress to become malignant and this review addresses how autophagy modulates cancer metastasis. Specifically, we examine the critical role played by autophagy in tumor cell migration and invasion, in maintaining the cancer stem cell phenotype and tumor cell dormancy as well as how autophagy affects interactions of tumor cells with components of the tumor microenvironment. Finally, we discuss how these functions make autophagy inhibition an attractive therapeutic option for metastatic cancers.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.14388