The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Metabolic Reprogramming of Cancer-Associated Fibroblasts by IDH3α Downregulation
Open accessAbstract
Cancer-associated fibroblasts (CAFs) provide critical metabolites for tumor growth and undergo metabolic reprogramming to support glycolysis. However, the molecular mechanisms responsible for this change remain unclear. Here, we report that TGF-β1- or PDGF-induced CAFs switch from oxidative phosphorylation to aerobic glycolysis. We identify downregulation of isocitrate dehydrogenase 3α (IDH3α) as a marker for this switch. Furthermore, miR-424 downregulates IDH3α during CAF formation. Downregulation of IDH3α decreases the effective level of α-ketoglutarate (α-KG) by reducing the ratio of α-KG to fumarate and succinate, resulting in PHD2 inhibition and HIF-1α protein stabilization. The accumulation of HIF-1α, in turn, promotes glycolysis by increasing the uptake of glucose, upregulating expression of glycolytic enzymes under normoxic conditions, and inhibiting oxidative phosphorylation by upregulating NDUFA4L2. CAFs from tumor samples exhibit low levels of IDH3α, and overexpression of IDH3α prevents transformation of fibroblasts into CAFs. Our studies reveal IDH3α to be a critical metabolic switch in CAFs.
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Cites
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Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium
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TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia
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Cited by
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265
The hypoxic tumour microenvironment
Petrova, V., Annicchiarico-Petruzzelli, M., Melino, G., & Amelio, I. (2018) · Oncogenesis · doi:10.1038/s41389-017-0011-9 · Cited by 1,019
Metabolic Interactions in the Tumor Microenvironment
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Metadata
- Authors
- Zhang, D., Wang, Y., Shi, Z., Liu, J., Sun, P., Hou, X., Zhang, J., Zhao, S., Zhou, B. P., & Mi, J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 10
- Issue
- 8
- Pages
- 1335-1348
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2127927969
- Cited by
- 333
- References
- 7
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zhang, D., Wang, Y., Shi, Z., Liu, J., Sun, P., Hou, X., Zhang, J., Zhao, S., Zhou, B. P., & Mi, J. (2015). Metabolic Reprogramming of Cancer-Associated Fibroblasts by IDH3α Downregulation. Cell Reports. https://doi.org/10.1016/j.celrep.2015.02.006
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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