The dynamic nature of autophagy in cancer.

By Alec C. Kimmelman. Genes & Development, 2011

606 citations recorded by the source corpus.

Macroautophagy (referred to hereafter as autophagy) is a highly regulated cellular process that serves to remove damaged proteins and organelles from the cell. Autophagy contributes to an array of normal and pathological processes, and has recently emerged as a key regulator of multiple aspects of cancer biology. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. This complexity is illustrated by the identification of settings where autophagy acts potently to either promote or inhibit tumorigenesis. In this review, I discuss the underlying basis for these opposing functions and propose a model suggesting a dynamic role for autophagy in malignancy. Collectively, the data point to autophagy as serving as a barrier to limit tumor initiation. Once neoplastic lesions are established, it appears that adaptive changes occur that now result in positive roles for autophagy in malignant progression and in subsequent tumor maintenance. Remarkably, constitutive activation of autophagy is critical for continued growth of some tumors, serving to both reduce oxidative stress and provide key intermediates to sustain cell metabolism. Autophagy is also induced in response to cancer therapies where it can function as a survival mechanism that limits drug efficacy. These findings have inspired significant interest in applying anti-autophagy therapies as an entirely new approach to cancer treatment. It is now apparent that aberrant control of autophagy is among the key hallmarks of cancer. While much needs to be learned about the regulation and context-dependent biological functions of autophagy, it seems clear that modulation of this process will be an attractive avenue for future cancer therapeutic approaches.

Subfields: Epidemiology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/6f2c12a317b3acee241b2514a5b8444087f61406

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Alec C. Kimmelman
2. E. White
3. Linda Partridge
4. T. Niccoli
5. J. Mancias
6. J. Harper
7. I. Slaninová
8. Guido Kroemer

In Pharmacology

1. E. White
2. Linda Partridge
3. T. Niccoli
4. Alec C. Kimmelman

Citations in the corpus

• KRAS: feeding pancreatic cancer proliferation (2014, neutral): “The role of autophagy in cancer is extremely complex as demonstrated by a growing literature describing situations where autophagy can either promote or inhibit tumorigenesis [58,59].”
• Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy (2014, background): “7f, lane 1 versus lanes 5 and 9).”
• Autophagy and Tumor Metabolism (2017, background): “Many tumor types demonstrate elevated basal autophagy and this can be seen in a cell autonomous manner, even under nutrient replete conditions (Kimmelman, 2011; White, 2015).”
• Ageing as a risk factor for disease. (2012, background): “Partial impairment of autophagy, on the other hand, promotes malignancy: human breast and ovarian cancers often show loss of one copy of the BECN1 gene, which only partly decreases autophagy, and mice heterozygous for BECN1 show an increase in benign and malignant tumours [114].”