Skip to main content

Main menu

  • Home
  • About
    • About CBM
    • Editorial Board
    • Announcement
  • Articles
    • Ahead of print
    • Current Issue
    • Archive
    • Collections
    • Cover Story
  • For Authors
    • Instructions for Authors
    • Resources
    • Submit a Manuscript
  • For Reviewers
    • Become a Reviewer
    • Instructions for Reviewers
    • Resources
    • Outstanding Reviewer
  • Subscription
  • Alerts
    • Email Alerts
    • RSS Feeds
    • Table of Contents
  • Contact us
  • Other Publications
    • cbm

User menu

  • My alerts

Search

  • Advanced search
Cancer Biology & Medicine
  • Other Publications
    • cbm
  • My alerts
Cancer Biology & Medicine

Advanced Search

 

  • Home
  • About
    • About CBM
    • Editorial Board
    • Announcement
  • Articles
    • Ahead of print
    • Current Issue
    • Archive
    • Collections
    • Cover Story
  • For Authors
    • Instructions for Authors
    • Resources
    • Submit a Manuscript
  • For Reviewers
    • Become a Reviewer
    • Instructions for Reviewers
    • Resources
    • Outstanding Reviewer
  • Subscription
  • Alerts
    • Email Alerts
    • RSS Feeds
    • Table of Contents
  • Contact us
  • Follow cbm on Twitter
  • Visit cbm on Facebook
Research ArticleOriginal Article
Open Access

Mitochondrial uncoupling inhibits serine catabolism via FTO activation in metastatic breast cancer

Xin Jin, Albert M. Li, Man Zhao, Haowen Jiang, Yiren Xiao, Michaela Yip, Stavros Melemenidis, Scott Jackson, Yanan Yang, Cathyrin Simmermaker, Meng-Ning Zhou, Subarna Sinha, Daniel J. Cuthbertson, Erinn B. Rankin and Jiangbin Ye
Cancer Biology & Medicine September 2026, 23 (9) 1303-1319; DOI: https://doi.org/10.20892/j.issn.2095-3941.2025.0444
Xin Jin
1Department of Oncology and Hematology, The Second Hospital of Jilin University, Changchun, Jilin 130000, China
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Albert M. Li
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
3Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Man Zhao
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haowen Jiang
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yiren Xiao
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michaela Yip
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stavros Melemenidis
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott Jackson
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yanan Yang
4Agilent Technologies, Santa Clara, CA 95051, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cathyrin Simmermaker
4Agilent Technologies, Santa Clara, CA 95051, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Meng-Ning Zhou
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Subarna Sinha
5Department of Computer Science, Stanford University, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel J. Cuthbertson
4Agilent Technologies, Santa Clara, CA 95051, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erinn B. Rankin
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
3Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA
6Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Erinn B. Rankin
  • For correspondence: erankin{at}stanford.edu jiangbinye{at}muhn.edu.cn
Jiangbin Ye
2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
3Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jiangbin Ye
  • For correspondence: erankin{at}stanford.edu jiangbinye{at}muhn.edu.cn
  • Article
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
Loading

References

  1. 1.↵
    1. Li AM,
    2. Ye J.
    The PHGDH enigma: do cancer cells only need serine or also a redox modulator? Cancer Lett. 2020; 476: 97–105.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Li AM,
    2. Ye J.
    Reprogramming of serine, glycine and one-carbon metabolism in cancer. Biochim Biophys Acta Mol Basis Dis. 2020; 1866: 165841.
  3. 3.↵
    1. Locasale JW.
    Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer. 2013; 13: 572–83.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.
    1. Yang M,
    2. Vousden KH.
    Serine and one-carbon metabolism in cancer. Nat Rev Cancer. 2016; 16: 650–62.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Fan J,
    2. Ye J,
    3. Kamphorst JJ,
    4. Shlomi T,
    5. Thompson CB,
    6. Rabinowitz JD.
    Quantitative flux analysis reveals folate-dependent NADPH production. Nature. 2014; 510: 298–302.
    OpenUrlCrossRefPubMedWeb of Science
  6. 6.↵
    1. Ducker GS,
    2. Rabinowitz JD.
    One-carbon metabolism in health and disease. Cell Metab. 2017; 25: 27–42.
    OpenUrlCrossRefPubMed
  7. 7.
    1. Zhu J,
    2. Berisa M,
    3. Schwörer S,
    4. Qin W,
    5. Cross JR,
    6. Thompson CB.
    Transsulfuration activity can support cell growth upon extracellular cysteine limitation. Cell Metab. 2019; 30: 865–76.e5.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Ducker GS,
    2. Chen L,
    3. Morscher RJ,
    4. Ghergurovich JM,
    5. Esposito M,
    6. Teng X, et al.
    Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway. Cell Metab. 2016; 23: 1140–53.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Tibbetts AS,
    2. Appling DR.
    Compartmentalization of mammalian folate-mediated one-carbon metabolism. Annu Rev Nutr. 2010; 30: 57–81.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    1. Chen L,
    2. Zhang Z,
    3. Hoshino A,
    4. Zheng HD,
    5. Morley M,
    6. Arany Z, et al.
    NADPH production by the oxidative pentose-phosphate pathway supports folate metabolism. Nat Metab. 2019; 1: 404–15.
    OpenUrlPubMed
  11. 11.↵
    1. Nilsson R,
    2. Jain M,
    3. Madhusudhan N,
    4. Sheppard NG,
    5. Strittmatter L,
    6. Kampf C, et al.
    Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer. Nat Commun. 2014; 5: 3128.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Ye J,
    2. Fan J,
    3. Venneti S,
    4. Wan YW,
    5. Pawel BR,
    6. Zhang J, et al.
    Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 2014; 4: 1406–17.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Li AM,
    2. Ducker GS,
    3. Li Y,
    4. Seoane JA,
    5. Xiao Y,
    6. Melemenidis S, et al.
    Metabolic profiling reveals a dependency of human metastatic breast cancer on mitochondrial serine and one-carbon unit metabolism. Mol Cancer Res. 2020; 18: 599–611.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Yang L,
    2. Garcia Canaveras JC,
    3. Chen Z,
    4. Wang L,
    5. Liang L,
    6. Jang C, et al.
    Serine catabolism feeds NADH when respiration is impaired. Cell Metab. 2020; 31: 809–21.e6.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Minn AJ,
    2. Gupta GP,
    3. Siegel PM,
    4. Bos PD,
    5. Shu W,
    6. Giri DD, et al.
    Genes that mediate breast cancer metastasis to lung. Nature. 2005; 436: 518–24.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Xiao Y,
    2. Thakkar KN,
    3. Zhao H,
    4. Broughton J,
    5. Li Y,
    6. Seoane JA, et al.
    The m6A RNA demethylase FTO is a HIF-independent synthetic lethal partner with the VHL tumor suppressor. Proc Natl Acad Sci U S A. 2020; 117: 21441–9.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Einstein JM,
    2. Perelis M,
    3. Chaim IA,
    4. Meena JK,
    5. Nussbacher JK,
    6. Tankka AT, et al.
    Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer. Mol Cell. 2021; 81: 3048–64.e9.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Clarke C,
    2. Madden SF,
    3. Doolan P,
    4. Aherne ST,
    5. Joyce H,
    6. O’Driscoll L, et al.
    Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis. Carcinogenesis. 2013; 34: 2300–8.
    OpenUrlCrossRefPubMedWeb of Science
  19. 19.↵
    1. Sabatier R,
    2. Finetti P,
    3. Adelaide J,
    4. Guille A,
    5. Borg JP,
    6. Chaffanet M, et al.
    Down-regulation of ECRG4, a candidate tumor suppressor gene, in human breast cancer. PLoS One. 2011; 6: e27656.
  20. 20.↵
    1. Alasadi A,
    2. Chen M,
    3. Swapna GVT,
    4. Tao H,
    5. Guo J,
    6. Collantes J, et al.
    Effect of mitochondrial uncouplers niclosamide ethanolamine (NEN) and oxyclozanide on hepatic metastasis of colon cancer. Cell Death Dis. 2018; 9: 215.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Kenwood BM,
    2. Weaver JL,
    3. Bajwa A,
    4. Poon IK,
    5. Byrne FL,
    6. Murrow BA, et al.
    Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab. 2014; 3: 114–23.
    OpenUrlPubMed
  22. 22.↵
    1. Jiang H,
    2. Greathouse RL,
    3. Tiche SJ,
    4. Zhao M,
    5. He B,
    6. Li Y, et al.
    Mitochondrial uncoupling induces epigenome remodeling and promotes differentiation in neuroblastoma. Cancer Res. 2023; 83: 181–94.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Jiang H,
    2. Tiche SJ,
    3. He CJ,
    4. Liu J,
    5. Bian F,
    6. Jedoui M, et al.
    Restoring mitochondrial quantity and quality to reverse the Warburg effect and drive neuroblastoma differentiation. Proc Natl Acad Sci U S A. 2025; 122: e2502483122.
  24. 24.↵
    1. Nikiforov MA,
    2. Chandriani S,
    3. O’Connell B,
    4. Petrenko O,
    5. Kotenko I,
    6. Beavis A, et al.
    A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism. Mol Cell Biol. 2002; 22: 5793–800.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Haggerty TJ,
    2. Zeller KI,
    3. Osthus RC,
    4. Wonsey DR,
    5. Dang CV.
    A strategy for identifying transcription factor binding sites reveals two classes of genomic c-Myc target sites. Proc Natl Acad Sci U S A. 2003; 100: 5313–8.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Xuan J,
    2. Chen L,
    3. Chen Z,
    4. Pang J,
    5. Huang J,
    6. Lin J, et al.
    RMBase v3.0: decode the landscape, mechanisms and functions of RNA modifications. Nucleic Acids Res. 2024; 52: D273–D84.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Wang P,
    2. Doxtader KA,
    3. Nam Y.
    Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Mol Cell. 2016; 63: 306–17.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Wang X,
    2. Feng J,
    3. Xue Y,
    4. Guan Z,
    5. Zhang D,
    6. Liu Z, et al.
    Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex. Nature. 2016; 534: 575–8.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Liu J,
    2. Yue Y,
    3. Han D,
    4. Wang X,
    5. Fu Y,
    6. Zhang L, et al.
    A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014; 10: 93–5.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Ping XL,
    2. Sun BF,
    3. Wang L,
    4. Xiao W,
    5. Yang X,
    6. Wang WJ, et al.
    Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014; 24: 177–89.
    OpenUrlCrossRefPubMedWeb of Science
  31. 31.↵
    1. Wen J,
    2. Lv R,
    3. Ma H,
    4. Shen H,
    5. He C,
    6. Wang J, et al.
    Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell self-renewal. Mol Cell. 2018; 69: 1028–38.e6.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Pendleton KE,
    2. Chen B,
    3. Liu K,
    4. Hunter OV,
    5. Xie Y,
    6. Tu BP, et al.
    The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell. 2017; 169: 824–35.e14.
    OpenUrlCrossRefPubMed
  33. 33.
    1. Doxtader KA,
    2. Wang P,
    3. Scarborough AM,
    4. Seo D,
    5. Conrad NK,
    6. Nam Y.
    Structural basis for regulation of METTL16, an S-adenosylmethionine homeostasis factor. Mol Cell. 2018; 71: 1001–11.e4.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Mendel M,
    2. Chen KM,
    3. Homolka D,
    4. Gos P,
    5. Pandey RR,
    6. McCarthy AA, et al.
    Methylation of structured RNA by the m6A writer METTL16 is essential for mouse embryonic development. Mol Cell. 2018; 71: 986–1000.e11.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Jia G,
    2. Fu Y,
    3. Zhao X,
    4. Dai Q,
    5. Zheng G,
    6. Yang Y, et al.
    N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011; 7: 885–7.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Huang H,
    2. Weng H,
    3. Sun W,
    4. Qin X,
    5. Shi H,
    6. Wu H, et al.
    Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018; 20: 285–95.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Cerneckis J,
    2. Ming GL,
    3. Song H,
    4. He C,
    5. Shi Y.
    The rise of epitranscriptomics: recent developments and future directions. Trends Pharmacol Sci. 2024; 45: 24–38.
    OpenUrlCrossRef
  38. 38.↵
    1. Roundtree IA,
    2. Evans ME,
    3. Pan T,
    4. He C.
    Dynamic RNA modifications in gene expression regulation. Cell. 2017; 169: 1187–200.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Pomaville MM,
    2. He C.
    Advances in targeting RNA modifications for anticancer therapy. Trends Cancer. 2023; 9: 528–42.
    OpenUrlPubMed
  40. 40.↵
    1. Zhao M,
    2. Zhang D,
    3. Jiang H,
    4. Kuganesan N,
    5. Natarajan S,
    6. Pu L, et al.
    The RNA demethylase FTO promotes glutamine metabolism in clear cell renal cell carcinoma through the regulation of SLC1A5. Sci Adv. 2025; 11: eadv2417.
  41. 41.↵
    1. Zheng G,
    2. Dahl JA,
    3. Niu Y,
    4. Fedorcsak P,
    5. Huang CM,
    6. Li CJ, et al.
    ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013; 49: 18–29.
    OpenUrlCrossRefPubMedWeb of Science
  42. 42.↵
    1. Su R,
    2. Dong L,
    3. Li C,
    4. Nachtergaele S,
    5. Wunderlich M,
    6. Qing Y, et al.
    R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling. Cell. 2018; 172: 90–105.e23.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Kundu A,
    2. Brinkley GJ,
    3. Nam H,
    4. Karki S,
    5. Kirkman R,
    6. Pandit M, et al.
    l-2-Hydroxyglutarate remodeling of the epigenome and epitranscriptome creates a metabolic vulnerability in kidney cancer models. J Clin Invest. 2024; 134: e171294.
  44. 44.↵
    1. Terunuma A,
    2. Putluri N,
    3. Mishra P,
    4. Mathe EA,
    5. Dorsey TH,
    6. Yi M, et al.
    MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Invest. 2014; 124: 398–412.
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Kusi M,
    2. Zand M,
    3. Lin LL,
    4. Chen M,
    5. Lopez A,
    6. Lin CL, et al.
    2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity. Cell Rep. 2022; 38: 110220.
  46. 46.↵
    1. Intlekofer AM,
    2. Dematteo RG,
    3. Venneti S,
    4. Finley LW,
    5. Lu C,
    6. Judkins AR, et al.
    Hypoxia induces production of L-2-hydroxyglutarate. Cell Metab. 2015; 22: 304–11.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Oldham WM,
    2. Clish CB,
    3. Yang Y,
    4. Loscalzo J.
    Hypoxia-mediated increases in L-2-hydroxyglutarate coordinate the metabolic response to reductive stress. Cell Metab. 2015; 22: 291–303.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Fan J,
    2. Teng X,
    3. Liu L,
    4. Mattaini KR,
    5. Looper RE,
    6. Vander Heiden MG, et al.
    Human phosphoglycerate dehydrogenase produces the oncometabolite D-2-hydroxyglutarate. ACS Chem Biol. 2015; 10: 510–6.
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Ye D,
    2. Guan KL,
    3. Xiong Y.
    Metabolism, activity, and targeting of D- and L-2-hydroxyglutarates. Trends Cancer. 2018; 4: 151–65.
    OpenUrlPubMed
  50. 50.↵
    1. Karthikeyan SK,
    2. Chandrashekar DS,
    3. Sahai S,
    4. Shrestha S,
    5. Aneja R,
    6. Singh R, et al.
    MammOnc-DB, an integrative breast cancer data analysis platform for target discovery. NPJ Breast Cancer. 2025; 11: 35.
    OpenUrlPubMed
  51. 51.↵
    1. Tao H,
    2. Zhang Y,
    3. Zeng X,
    4. Shulman GI,
    5. Jin S.
    Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med. 2014; 20: 1263–9.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Zhao Y,
    2. Wang A,
    3. Zou Y,
    4. Su N,
    5. Loscalzo J,
    6. Yang Y.
    In vivo monitoring of cellular energy metabolism using SoNar, a highly responsive sensor for NAD+/NADH redox state. Nat Protoc. 2016; 11: 1345–59.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. Bagatell R,
    2. Park JR,
    3. Acharya S,
    4. Aldrink J,
    5. Allison J,
    6. Alva E, et al.
    Neuroblastoma, version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024; 22: 413–33.
    OpenUrlPubMed
  54. 54.↵
    1. Yang R,
    2. Guo Z,
    3. Li B.
    NADH reductive stress drives metabolic reprogramming. Trends Cell Biol. 2025. DOI: 10.1016/j.tcb.2025.07.005.
    OpenUrlCrossRef
  55. 55.↵
    1. Zhao Y,
    2. Hu Q,
    3. Cheng F,
    4. Su N,
    5. Wang A,
    6. Zou Y, et al.
    SoNar, a highly responsive NAD+/NADH sensor, allows high-throughput metabolic screening of anti-tumor agents. Cell Metab. 2015; 21: 777–89.
    OpenUrlCrossRefPubMed
  56. 56.↵
    1. Gaude E,
    2. Schmidt C,
    3. Gammage PA,
    4. Dugourd A,
    5. Blacker T,
    6. Chew SP, et al.
    NADH shuttling couples cytosolic reductive carboxylation of glutamine with glycolysis in cells with mitochondrial dysfunction. Mol Cell. 2018; 69: 581–93.e7.
    OpenUrlCrossRefPubMed
  57. 57.↵
    1. Possemato R,
    2. Marks KM,
    3. Shaul YD,
    4. Pacold ME,
    5. Kim D,
    6. Birsoy K, et al.
    Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011; 476: 346–50.
    OpenUrlCrossRefPubMedWeb of Science
  58. 58.
    1. Locasale JW,
    2. Grassian AR,
    3. Melman T,
    4. Lyssiotis CA,
    5. Mattaini KR,
    6. Bass AJ, et al.
    Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet. 2011; 43: 869–74.
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Ye J,
    2. Mancuso A,
    3. Tong X,
    4. Ward PS,
    5. Fan J,
    6. Rabinowitz JD, et al.
    Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A. 2012; 109: 6904–9.
    OpenUrlAbstract/FREE Full Text
  60. 60.↵
    1. Kamphorst JJ,
    2. Nofal M,
    3. Commisso C,
    4. Hackett SR,
    5. Lu W,
    6. Grabocka E, et al.
    Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res. 2015; 75: 544–53.
    OpenUrlAbstract/FREE Full Text
  61. 61.↵
    1. Pan M,
    2. Reid MA,
    3. Lowman XH,
    4. Kulkarni RP,
    5. Tran TQ,
    6. Liu X, et al.
    Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nat Cell Biol. 2016; 18: 1090–101.
    OpenUrlCrossRefPubMed
  62. 62.↵
    1. Jiang H,
    2. Jedoui M,
    3. Ye J.
    The Warburg effect drives dedifferentiation through epigenetic reprogramming. Cancer Biol Med. 2023; 20: 891–7.
    OpenUrlFREE Full Text
  63. 63.↵
    1. Jiang H,
    2. Ye J.
    The Warburg effect: the hacked mitochondrial-nuclear communication in cancer. Semin Cancer Biol. 2025; 112: 93–111.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Jiang H,
    2. Li AM,
    3. Ye J.
    The magic bullet: niclosamide. Front Oncol. 2022; 12: 1004978.
  65. 65.↵
    1. Jiang H,
    2. He CJ,
    3. Li AM,
    4. He B,
    5. Li Y,
    6. Zhou MN, et al.
    Mitochondrial uncoupling inhibits reductive carboxylation in cancer cells. Mol Cancer Res. 2023; 21: 1010–6.
    OpenUrlCrossRefPubMed
  66. 66.↵
    1. Jeschke J,
    2. Collignon E,
    3. Al Wardi C,
    4. Krayem M,
    5. Bizet M,
    6. Jia Y, et al.
    Downregulation of the FTO m6A RNA demethylase promotes EMT-mediated progression of epithelial tumors and sensitivity to Wnt inhibitors. Nat Cancer. 2021; 2: 611–28.
    OpenUrlPubMed
  67. 67.↵
    1. Zhang S,
    2. Zhang N,
    3. Wan T,
    4. He Y,
    5. Hao J,
    6. Liu Y, et al.
    Oncometabolite D-2HG drives tumor metastasis and protumoral macrophage polarization by targeting FTO/m6A/ANGPTL4/integrin axis in triple-negative breast cancer. J Exp Clin Cancer Res. 2025; 44: 41.
    OpenUrlPubMed
  68. 68.↵
    1. Schweizer MT,
    2. Haugk K,
    3. McKiernan JS,
    4. Gulati R,
    5. Cheng HH,
    6. Maes JL, et al.
    A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer. PLoS One. 2018; 13: e0198389.
  69. 69.↵
    1. Shah DP,
    2. Vancuylenburg CS,
    3. Olzomer EM,
    4. Chen SY,
    5. Grams RJ,
    6. Beretta M, et al.
    Diverse actions of 15 structurally unrelated mitochondrial uncouplers in cells and mice. Mol Metab. 2025; 99: 102204.
  70. 70.↵
    1. Jiang H,
    2. Macorano A,
    3. Xing E,
    4. Jedoui M,
    5. Mohammed S,
    6. Lee V, et al.
    Discovery of niclosamide analogs with potent mitochondrial uncoupling activity and reduced mitochondrial inhibition–associated toxicity. ACS Med Chem Lett. 2025: DOI: 10.1021/acsmedchemlett.5c00439.
    OpenUrlCrossRef
PreviousNext
Back to top

In this issue

Cancer Biology & Medicine: 23 (9)
Cancer Biology & Medicine
Vol. 23, Issue 9
15 Sep 2026
  • Table of Contents
  • Index by author
Print
Download PDF
Email Article

Thank you for your interest in spreading the word on Cancer Biology & Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Mitochondrial uncoupling inhibits serine catabolism via FTO activation in metastatic breast cancer
(Your Name) has sent you a message from Cancer Biology & Medicine
(Your Name) thought you would like to see the Cancer Biology & Medicine web site.
Citation Tools
Mitochondrial uncoupling inhibits serine catabolism via FTO activation in metastatic breast cancer
Xin Jin, Albert M. Li, Man Zhao, Haowen Jiang, Yiren Xiao, Michaela Yip, Stavros Melemenidis, Scott Jackson, Yanan Yang, Cathyrin Simmermaker, Meng-Ning Zhou, Subarna Sinha, Daniel J. Cuthbertson, Erinn B. Rankin, Jiangbin Ye
Cancer Biology & Medicine Sep 2026, 23 (9) 1303-1319; DOI: 10.20892/j.issn.2095-3941.2025.0444

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Mitochondrial uncoupling inhibits serine catabolism via FTO activation in metastatic breast cancer
Xin Jin, Albert M. Li, Man Zhao, Haowen Jiang, Yiren Xiao, Michaela Yip, Stavros Melemenidis, Scott Jackson, Yanan Yang, Cathyrin Simmermaker, Meng-Ning Zhou, Subarna Sinha, Daniel J. Cuthbertson, Erinn B. Rankin, Jiangbin Ye
Cancer Biology & Medicine Sep 2026, 23 (9) 1303-1319; DOI: 10.20892/j.issn.2095-3941.2025.0444
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and methods
    • Results
    • Discussion
    • Conclusions
    • Supporting Information
    • Conflict of interest statement
    • Declaration of generative AI and AI-assisted technologies in the writing process
    • Author contributions
    • Data availability statement
    • Acknowledgments
    • References
  • Figures & Data
  • Info & Metrics
  • References
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Efbemalenograstim alfa as prophylaxis for chemotherapy-induced neutropenia in patients with non–small-cell lung cancer: a randomized, multicenter, phase II trial
  • FDX1 expression promotes DSF/Cu-induced cuproptosis in gastric cancer cells
Show more Original Article

Similar Articles

Keywords

  • Mitochondria uncoupler
  • serine catabolism
  • one-carbon unit metabolism
  • FTO
  • m6A
  • breast cancer
  • metastasis

Navigate

  • Home
  • Current Issue

More Information

  • About CBM
  • About CACA
  • About TMUCIH
  • Editorial Board
  • Subscription

For Authors

  • Instructions for authors
  • Journal Policies
  • Submit a Manuscript

Journal Services

  • Email Alerts
  • Facebook
  • RSS Feeds
  • Twitter

 

© 2026 Cancer Biology & Medicine

Powered by HighWire