Dual role of autophagy in hallmarks of cancer
Abstract
Evolutionarily conserved across eukaryotic cells, macroautophagy (herein autophagy) is an intracellular catabolic degradative process targeting damaged and superfluous cellular proteins, organelles, and other cytoplasmic components. Mechanistically, it involves formation of double-membrane vesicles called autophagosomes that capture cytosolic cargo and deliver it to lysosomes, wherein the breakdown products are eventually recycled back to the cytoplasm. Dysregulation of autophagy often results in various disease manifestations, including neurodegeneration, microbial infections, and cancer. In the case of cancer, extensive attention has been devoted to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion. In this review, while we summarize how this self-eating process is implicated at various stages of tumorigenesis, most importantly, we address the link between autophagy and hallmarks of cancer. This would eventually provide a better understanding of tumor dependence on autophagy. We also discuss how therapeutics targeting autophagy can counter various transformations involved in tumorigenesis. Finally, this review will provide a novel insight into the mutational landscapes of autophagy-related genes in several human cancers, using genetic information collected from an array of cancers.
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Normally, autophagy plays a tumor suppressive role by preventing the accumulation of misfolded proteins, damaged organelles, and reactive oxygen species (ROS).
“Normally, autophagy plays a tumor suppressive role by preventing the accumulation of misfolded proteins, damaged organelles, and reactive oxygen species (ROS) [54].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [54]
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The Roles of Autophagy in Cancer
Yun, C. W., & Lee, S. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113466 · Cited by 965 · see citing works
Hypoxia and Selective Autophagy in Cancer Development and Therapy
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Quality Control of Orphaned Proteins
Juszkiewicz, S., & Hegde, R. S. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.001 · Cited by 165 · see citing works
Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer
Haynes, J., & Manogaran, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051988 · Cited by 82 · see citing works
“Normally, autophagy plays a tumor suppressive role by preventing the accumulation of misfolded proteins, damaged organelles, and reactive oxygen species (ROS) [54].”
Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance
Manzoor, S., Muhammad, J. S., Maghazachi, A. A., & Hamid, Q. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.924290 · Cited by 45 · see citing works
- Authors
- Singh, S. S., Vats, S., Chia, A. Y.-Q., Tan, T. Z., Deng, S., Ong, M. S., Arfuso, F., Yap, C. T., Goh, B. C., Sethi, G., Huang, R. Y.-J., Shen, H. M., Manjithaya, R., & Kumar, A. P.
- Affiliations
- National University of Singapore (SG)
- Jawaharlal Nehru Centre for Advanced Scientific Research (IN)
- Curtin University (AU)
- Corresponding author
- Manjithaya, Ravi
- Kumar, Alan Prem
- ORCID
- Venue
- Oncogene
- Published
- 2017-12-19
- Volume
- 37
- Issue
- 9
- Pages
- 1142-1158
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2772927056
- Cited by
- 542
- References
- 138
- Citations by year
- 2026: 20 · 2025: 44 · 2024: 58 · 2023: 62 · 2022: 75 · 2021: 90 · 2020: 100 · 2019: 53 · 2018: 40
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Research Foundation Singapore
- National Medical Research Council
- Cancer Science Institute of Singapore, National University of Singapore
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy, cancer hallmarks, carcinogenesis, tumor suppression, tumor promotion, autophagy-related genes, autophagosomes, lysosomal degradation, cancer genomics
- MeSH terms
- Animals, Autophagy, Cell Transformation, Neoplastic, Humans, Neoplasms
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