ArticleThe Journal of clinical investigation2015
Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 108 citations in OpenAlex.
- Decoding the metabolic‑immune crosstalk: The role of glutamine and ammonium reprogramming in prostate cancer immune evasion (Review).Oncology reports · 2026Review
- Cigarette smoke induces FASN-dependent fatty acid metabolic rewiring to drive bladder cancer progression.Cancer letters · 2026Article
- Steroid receptor coactivators: from basic research to translational opportunities.Endocrine reviews · 2026Review
- NNMT Loss Drives Cancer Progression by enhancing SAM availability for mTORC1 Signaling and Chromatin Methylation.bioRxiv : the preprint server for biology · 2026Article
- Nuclear-specific reductive carboxylation of alpha-ketoglutarate fuels histone acetylation to induce chromatin accessibility and gene activation.Nature communications · 2026Article
- Steroid receptor coactivators in immunity - From function to emerging translational opportunities.The Journal of biological chemistry · 2026Review
- NCOA2 promotes the return of hematopoietic stem cells to quiescence after irradiation stress by regulating FOXO3a-dependent mitophagy.HemaSphere · 2026Article
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Contrasting Effects of Clozapine and Risperidone on Cholesterol Metabolism, Synaptic Proteins, and Transcriptional Regulation in Human LUHMES Neurons.Molecular neurobiology · 2025Article
- Fueling Prostate Cancer: The Central Role of Glutamine/Glutamate Metabolic Reprogramming.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- Metabolic reprogramming and functional crosstalk within the tumor microenvironment (TME) and A Multi-omics anticancer approach.Medical oncology (Northwood, London, England) · 2025Review
- IDH status dictates oHSV mediated metabolic reprogramming affecting anti-tumor immunity.Nature communications · 2025Article
- The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma.Cell death discovery · 2025Review
- Cellular Signaling of Amino Acid Metabolism in Prostate Cancer.International journal of molecular sciences · 2025Review
- Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.Frontiers in oncology · 2025Review
- Interconnected study of molecular pathways: miR-137 as a central element at the intersection of lipid metabolism and prostate carcinogenesis.Einstein (Sao Paulo, Brazil) · 2025Article
- Tai/NCOA2 suppresses the Hedgehog pathway by directly targeting the transcription factor Ci/GLI.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer.JCI insight · 2024Article
- Complex I activity in hypoxia: implications for oncometabolism.Biochemical Society transactions · 2024Review
- Steroid receptor coactivators in Treg and Th17 cell biology and function.Frontiers in immunology · 2024Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2-driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.