Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell Carcinoma Article Swipe
Edward L. LaGory
,
Colleen Wu
,
Cullen M. Taniguchi
,
Chien‐Kuang Cornelia Ding
,
Jen‐Tsan Chi
,
Rie von Eyben
,
David A. Scott
,
Adam Richardson
,
Amato J. Giaccia
·
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2015.06.006
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2015.06.006
Long believed to be a byproduct of malignant transformation, reprogramming of cellular metabolism is now recognized as a driving force in tumorigenesis. In clear cell renal cell carcinoma (ccRCC), frequent activation of HIF signaling induces a metabolic switch that promotes tumorigenesis. Here, we demonstrate that PGC-1α, a central regulator of energy metabolism, is suppressed in VHL-deficient ccRCC by a HIF/Dec1-dependent mechanism. In VHL wild-type cells, PGC-1α suppression leads to decreased expression of the mitochondrial transcription factor Tfam and impaired mitochondrial respiration. Conversely, PGC-1α expression in VHL-deficient cells restores mitochondrial function and induces oxidative stress. ccRCC cells expressing PGC-1α exhibit impaired tumor growth and enhanced sensitivity to cytotoxic therapies. In patients, low levels of PGC-1α expression are associated with poor outcome. These studies demonstrate that suppression of PGC-1α recapitulates key metabolic phenotypes of ccRCC and highlight the potential of targeting PGC-1α expression as a therapeutic modality for the treatment of ccRCC.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.celrep.2015.06.006
- OA Status
- gold
- Cited By
- 181
- References
- 52
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W1756959975
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W1756959975Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.celrep.2015.06.006Digital Object Identifier
- Title
-
Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell CarcinomaWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2015Year of publication
- Publication date
-
2015-06-25Full publication date if available
- Authors
-
Edward L. LaGory, Colleen Wu, Cullen M. Taniguchi, Chien‐Kuang Cornelia Ding, Jen‐Tsan Chi, Rie von Eyben, David A. Scott, Adam Richardson, Amato J. GiacciaList of authors in order
- Landing page
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https://doi.org/10.1016/j.celrep.2015.06.006Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1016/j.celrep.2015.06.006Direct OA link when available
- Concepts
-
Reprogramming, Oxidative phosphorylation, Oxidative metabolism, Metabolism, Oxidative damage, Renal cell carcinoma, Cell biology, Oxidative stress, Biology, Cancer research, Cell, Chemistry, Internal medicine, Endocrinology, Biochemistry, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
181Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 22, 2024: 21, 2023: 14, 2022: 19, 2021: 17Per-year citation counts (last 5 years)
- References (count)
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52Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.demonstrate | 43, 122 |
| abstract_inverted_index.metabolism, | 51 |
| abstract_inverted_index.sensitivity | 104 |
| abstract_inverted_index.suppression | 66, 124 |
| abstract_inverted_index.therapeutic | 143 |
| abstract_inverted_index.respiration. | 80 |
| abstract_inverted_index.VHL-deficient | 55, 85 |
| abstract_inverted_index.mitochondrial | 73, 79, 88 |
| abstract_inverted_index.recapitulates | 127 |
| abstract_inverted_index.reprogramming | 9 |
| abstract_inverted_index.transcription | 74 |
| abstract_inverted_index.tumorigenesis. | 21, 40 |
| abstract_inverted_index.transformation, | 8 |
| abstract_inverted_index.HIF/Dec1-dependent | 59 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.550000011920929 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.96150905 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |