Growth factor regulation of autophagy and cell survival in the absence of apoptosis
Open accessAbstract
In animals, cells are dependent on extracellular signals to prevent apoptosis. However, using growth factor-dependent cells from Bax/Bak-deficient mice, we demonstrate that apoptosis is not essential to limit cell autonomous survival. Following growth factor withdrawal, Bax-/-Bak-/- cells activate autophagy, undergo progressive atrophy, and ultimately succumb to death. These effects result from loss of the ability to take up sufficient nutrients to maintain cellular bioenergetics. Despite abundant extracellular nutrients, growth factor-deprived cells maintain ATP production from catabolism of intracellular substrates through autophagy. Autophagy is essential for maintaining cell survival following growth factor withdrawal and can sustain viability for several weeks. During this time, cells respond to growth factor readdition by rapid restoration of the ability to take up and metabolize glucose and by subsequent recovery of their original size and proliferative potential. Thus, growth factor signal transduction is required to direct the utilization of sufficient exogenous nutrients to maintain cell viability.
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Autophagy allows nutrient- or growth factor-deprived cells to maintain viability in culture for weeks.
“autophagy allows nutrient- or growth factor-deprived cells to maintain their viability in culture for weeks”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Lum et al., 2005
Growth factor-induced signaling coordinates metabolism to meet the rising demands of proliferation, including maintaining a bioenergetic state permissive for growth.
“Growth factor-induced signaling coordinates these functions, including maintaining a bioenergetic state permissive for growth (Lum et al, 2005).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Lum et al, 2005
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- Authors
- Lum, J. J., Bauer, D. E., Kong, M., Harris, M. H., Li, C., Lindsten, T., & Thompson, C. B.
- Affiliations
- Abramson Cancer Center (US)
- Corresponding author
- Thompson, Craig B.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 120
- Issue
- 2
- Pages
- 237-248
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1970101770
- Cited by
- 1,487
- References
- 50
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 41 · 2023: 40 · 2022: 42 · 2021: 40 · 2020: 58 · 2019: 58 · 2018: 63 · 2017: 74 · 2016: 78 · 2015: 86 · 2014: 82 · 2013: 115 · 2012: 109
- FWCI
- 71.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- autophagy, cell survival, growth factor withdrawal, apoptosis, nutrient uptake, cellular bioenergetics, glucose metabolism, growth factor signaling, cell proliferation, cell size
- MeSH terms
- Animals, Autophagy, Bone Marrow Cells, Glycolysis, Growth Substances, Interleukin-3, Lysosomes, Mitochondria, Apoptosis, Mice, Knockout, Proto-Oncogene Proteins c-bcl-2, Microscopy, Electron, Transmission, bcl-2-Associated X Protein, Mice, DNA Fragmentation
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