Fatty acid uptake and lipid storage induced by HIF-1α contribute to cell growth and survival after hypoxia-reoxygenation.

By K. Bensaad, E. Favaro, C. Lewis, B. Peck, S. Lord, Jennifer M. Collins, Katherine E. Pinnick, S. Wigfield, F. Buffa, Ji-Liang Li and 5 more. Cell Reports, 2014

610 citations recorded by the source corpus.

An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo.

Subfields: Biochemistry, Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/02cac455136e68b14945f867a314078cb1cf66b4

How researchers see this paper

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In Biochemistry

1. Nikos Koundouros
2. G. Poulogiannis
3. A. Schulze

In Cancer Research

1. Eyal Gottlieb
2. G. Poulogiannis
3. Nikos Koundouros
4. Adrian L. Harris
5. A. Schulze
6. G. Semenza

In Molecular Biology

1. Eyal Gottlieb
2. Nikos Koundouros
3. Adrian L. Harris
4. A. Schulze
5. G. Poulogiannis

Citations in the corpus

• Reprogramming of fatty acid metabolism in cancer (2019, background): “Indeed, knockdown of FABP3 and FABP7 decreases the growth of U87 glioblastoma tumours in vivo, an effect largely attributable to reduced FA uptake and inhibition of LD formation.(21) On a broader level, delineating the mechanisms driving interactions between cancer cells and adipocytes has provided ”
• Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress (2015, background): “Altogether, these results indicate that metabolic stress induces major changes in the lipid metabolism landscape of cancer cells, creating a dependence on de novo lipogenesis for survival in hypoxia/low serum (Ackerman and Simon, 2014; Bensaad et al., 2014).”
• Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila (2015, neutral): “In a mammalian example, hypoxia induces lipid droplets in glioblastoma and breast cancer cells via a pathway involving HIF-1a (Bensaad et al., 2014).”