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NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling

Oncogene volume 42, pages 808–824 (2023)Cite this article

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Abstract

NAD+ levels decline with age and in certain disease conditions. NAD+ precursors have been shown to stimulate NAD+ biosynthesis and ameliorate various age-associated diseases in mouse models. However, NAD+ metabolism is complicated in cancer and its role in triple-negative breast cancer (TNBC) remains elusive. Here, we show that NAD+ supplement suppresses tumor metastasis in a TNBC orthotopic patient-derived xenograft (PDX) model. Sirtuin1 lysine deacetylase (SIRT1) is required for the effects since SIRT1 knockdown blocks NAD+-suppressed tumor metastasis. Overexpression of SIRT1 effectively impairs the metastatic potential of TNBC. Importantly, the interaction between SIRT1 and p66Shc causes the deacetylation and functional inactivation of p66Shc, which inhibits epithelial-mesenchymal transition (EMT). Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.

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Fig. 1: NAD+ supplementation suppresses TNBC progression.
Fig. 2: The expression of SIRT1 in clinical samples and TNBC cells.
Fig. 3: SIRT1 suppresses the invasive ability of TNBC cells and tumor metastasis.
Fig. 4: Targeting SIRT1 blocks NAD+-inhibited tumor metastasis.
Fig. 5: SIRT1 interacts with P66Shc and mediates its acetylation and phosphorylation.
Fig. 6: NAD+ metabolism regulates the acetylation and phosphorylation of P66Shc via SIRT1.
Fig. 7: NAD+ supplementation suppresses tumor metastasis by regulating the SIRT1/P66Shc signaling and EMT process.
Fig. 8: A proposed model depicting that NAD+ supplementation induces SIRT1 activation in TNBC.

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Data availability

The RNA sequence data in the present study have been deposited in the NCBI Gene Expression Omnibus (GEO) public database with the accession number GSE220683. All data are available from the authors upon reasonable request.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Prim. 2019;5:66.

    Article  PubMed  Google Scholar 

  3. Harbeck N, Gnant M. Breast cancer. Lancet. 2017;389:1134–50.

    Article  PubMed  Google Scholar 

  4. Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer—the road to new treatment strategies. Lancet. 2017;389:2430–42.

    Article  CAS  PubMed  Google Scholar 

  5. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321:288–300.

    Article  CAS  PubMed  Google Scholar 

  6. Yoshino J, Baur JA, Imai SI. NAD(+) intermediates: the biology and therapeutic potential of NMN and NR. Cell Metab. 2018;27:513–28.

    Article  CAS  PubMed  Google Scholar 

  7. Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24:795–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Canto C, Menzies KJ, Auwerx J. NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 2015;22:31–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, et al. Circadian clock feedback cycle through NAMPT-mediated NAD(+) biosynthesis. Science. 2009;324:651–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhu XH, Lu M, Lee BY, Ugurbil K, Chen W. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci USA. 2015;112:2876–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14:528–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, et al. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J Biol Chem. 2002;277:18881–90.

    Article  CAS  PubMed  Google Scholar 

  13. Balan V, Miller GS, Kaplun L, Balan K, Chong ZZ, Li F, et al. Life span extension and neuronal cell protection by Drosophila nicotinamidase. J Biol Chem. 2008;283:27810–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Canto C, et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, et al. NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5:227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Navas LE, Carnero A. NAD(+) metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther. 2021;6:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. Circadian control of the NAD(+) salvage pathway by CLOCK-SIRT1. Science. 2009;324:654–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305:390–2.

    Article  CAS  PubMed  Google Scholar 

  19. Blander G, Guarente L. The Sir2 family of protein deacetylases. Annu Rev Biochem. 2004;73:417–35.

    Article  CAS  PubMed  Google Scholar 

  20. Finkel T, Deng CX, Mostoslavsky R. Recent progress in the biology and physiology of sirtuins. Nature. 2009;460:587–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Satoh A, Brace CS, Rensing N, Cliften P, Wozniak DF, Herzog ED, et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 2013;18:416–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Scheibye-Knudsen M, Mitchell SJ, Fang EF, Iyama T, Ward T, Wang J, et al. A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014;20:840–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, et al. Sirt1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012;15:675–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127:1109–22.

    Article  CAS  PubMed  Google Scholar 

  26. Herranz D, Munoz-Martin M, Canamero M, Mulero F, Martinez-Pastor B, Fernandez-Capetillo O, et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun. 2010;1:3.

    Article  PubMed  Google Scholar 

  27. Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci USA. 2008;105:9793–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Guarente L. Sirtuins, aging, and medicine. N Engl J Med. 2011;364:2235–44.

    Article  CAS  PubMed  Google Scholar 

  29. Chalkiadaki A, Guarente L. The multifaceted functions of sirtuins in cancer. Nat Rev Cancer. 2015;15:608–24.

    Article  CAS  PubMed  Google Scholar 

  30. Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 2005;123:437–48.

    Article  CAS  PubMed  Google Scholar 

  31. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, et al. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008;135:907–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008;14:312–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Das A, Huang GX, Bonkowski MS, Longchamp A, Li C, Schultz MB, et al. Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging. Cell. 2018;173:74–89.e20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, et al. NAD(+) replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab. 2016;24:566–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nayagam VM, Wang X, Tan YC, Poulsen A, Goh KC, Ng T, et al. Sirt1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents. J Biomol Screen. 2006;11:959–67.

    Article  CAS  PubMed  Google Scholar 

  36. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191–6.

    Article  CAS  PubMed  Google Scholar 

  37. Solomon JM, Pasupuleti R, Xu L, McDonagh T, Curtis R, DiStefano PS, et al. Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol Cell Biol. 2006;26:28–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sanchez-Perez P, Cadenas S, et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015;6:183–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, et al. Dynamic ROS control by TIGAR regulates the initiation and progression of pancreatic cancer. Cancer Cell. 2020;37:168–82.e164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Porporato PE, Payen VL, Perez-Escuredo J, De Saedeleer CJ, Danhier P, Copetti T, et al. A mitochondrial switch promotes tumor metastasis. Cell Rep. 2014;8:754–66.

    Article  CAS  PubMed  Google Scholar 

  41. Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboidl P, Pandolfi PP, et al. The p66(shc) adaptor protein controls oxidative stress response and life span in mammals. Nature. 1999;402:309–13.

    Article  CAS  PubMed  Google Scholar 

  42. Giorgio M, Migliaccio E, Orsini F, Paolucci D, Moroni M, Contursi C, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell. 2005;122:221–33.

    Article  CAS  PubMed  Google Scholar 

  43. Kumar S, Kim YR, Vikram A, Naqvi A, Li Q, Kassan M, et al. Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction. Proc Natl Acad Sci USA. 2017;114:1714–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc Natl Acad Sci USA. 2005;102:11278–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lewis K, Kiepas A, Hudson J, Senecal J, Ha JR, Voorand E, et al. P66ShcA functions as a contextual promoter of breast cancer metastasis. Breast Cancer Res. 2020;22:7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Verdin E. NAD(+) in aging, metabolism, and neurodegeneration. Science. 2015;350:1208–13.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352:1436–43.

    Article  CAS  PubMed  Google Scholar 

  48. Braidy N, Berg J, Clement J, Khorshidi F, Poljak A, Jayasena T, et al. Role of nicotinamide adenine dinucleotide and related precursors as therapeutic targets for age-related degenerative diseases: rationale, biochemistry, pharmacokinetics, and outcomes. Antioxid Redox Signal. 2019;30:251–94.

    Article  CAS  PubMed  Google Scholar 

  49. Lv H, Lv G, Chen C, Zong Q, Jiang G, Ye D, et al. NAD(+) metabolism maintains inducible PD-L1 expression to drive tumor immune evasion. Cell Metab. 2021;33:110–27.e115.

    Article  CAS  PubMed  Google Scholar 

  50. Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, LeBoeuf SE, Gay LJ, et al. Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest. 2013;123:1068–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yoo KH, Tang JJ, Rashid MA, Cho CH, Corujo-Ramirez A, Choi J, et al. Nicotinamide mononucleotide prevents cisplatin-induced cognitive impairments. Cancer Res. 2021;81:3727–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S, et al. NAD(+) metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol. 2019;21:397–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang Y, Wang F, Wang L, Qiu S, Yao Y, Yan C, et al. NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells. Cell Rep. 2021;36:109516.

    Article  CAS  PubMed  Google Scholar 

  54. Guan Y, Wang SR, Huang XZ, Xie QH, Xu YY, Shang D, et al. Nicotinamide mononucleotide, an NAD(+) precursor, rescues age-associated susceptibility to AKI in a sirtuin 1-dependent manner. J Am Soc Nephrol. 2017;28:2337–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Byles V, Zhu L, Lovaas JD, Chmilewski LK, Wang J, Faller DV, et al. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis. Oncogene. 2012;31:4619–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sun T, Jiao L, Wang Y, Yu Y, Ming L. SIRT1 induces epithelial-mesenchymal transition by promoting autophagic degradation of E-cadherin in melanoma cells. Cell Death Dis. 2018;9:136.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Cheng F, Su L, Yao C, Liu L, Shen J, Liu C, et al. SIRT1 promotes epithelial-mesenchymal transition and metastasis in colorectal cancer by regulating Fra-1 expression. Cancer Lett. 2016;375:274–83.

    Article  CAS  PubMed  Google Scholar 

  58. Simic P, Williams EO, Bell EL, Gong JJ, Bonkowski M, Guarente L. SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis. Cell Rep. 2013;3:1175–86.

    Article  CAS  PubMed  Google Scholar 

  59. Shi L, Tang X, Qian M, Liu Z, Meng F, Fu L, et al. A SIRT1-centered circuitry regulates breast cancer stemness and metastasis. Oncogene. 2018;37:6299–315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Latifkar A, Ling L, Hingorani A, Johansen E, Clement A, Zhang X, et al. Loss of sirtuin 1 alters the secretome of breast cancer cells by impairing lysosomal integrity. Dev Cell. 2019;49:393–408.e397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang RH, Zheng Y, Kim HS, Xu X, Cao L, Luhasen T, et al. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol Cell. 2008;32:11–20.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493–506.

    Article  CAS  PubMed  Google Scholar 

  63. Dolfini E, Roncoroni L, Dogliotti E, Sala G, Erba E, Sacchi N, et al. Resveratrol impairs the formation of MDA-MB-231 multicellular tumor spheroids concomitant with ceramide accumulation. Cancer Lett. 2007;249:143–7.

    Article  CAS  PubMed  Google Scholar 

  64. Jackson JG, Yoneda T, Clark GM, Yee D. Elevated levels of p66 Shc are found in breast cancer cell lines and primary tumors with high metastatic potential. Clin Cancer Res. 2000;6:1135–9.

    CAS  PubMed  Google Scholar 

  65. Davol PA, Bagdasaryan R, Elfenbein GJ, Maizel AL, Frackelton AR. Shc proteins are strong, independent prognostic markers for both node-negative and node-positive primary breast cancer. Cancer Res. 2003;63:6772–83.

    CAS  PubMed  Google Scholar 

  66. Frackelton AR Jr, Lu L, Davol PA, Bagdasaryan R, Hafer LJ, Sgroi DC. P66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy. Breast Cancer Res. 2006;8:R73.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Furlan T, Khalid S, Nguyen AV, Gunther J, Troppmair J. The oxidoreductase p66Shc acts as tumor suppressor in BRAFV600E-transformed cells. Mol Oncol. 2018;12:869–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lebiedzinska-Arciszewska M, Oparka M, Vega-Naredo I, Karkucinska-Wieckowska A, Pinton P, Duszynski J, et al. The interplay between p66Shc, reactive oxygen species and cancer cell metabolism. Eur J Clin Investig. 2015;45:25–31.

    Article  CAS  Google Scholar 

  69. Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013;12:931–47.

    Article  CAS  PubMed  Google Scholar 

  70. Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Reactive oxygen species and cancer paradox: to promote or to suppress? Free Radic Biol Med. 2017;104:144–64.

    Article  CAS  PubMed  Google Scholar 

  71. Zhang X, Lewis MT. Establishment of patient-derived xenograft (PDX) models of human breast cancer. Curr Protoc Mouse Biol. 2013;3:21–9.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank all the staff members of Luo laboratory for their technical support and critical suggestions. This work was supported by the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (No. 20181821569) and the Self-Topic Fund of Tsinghua University (No. 20191080585).

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Authors and Affiliations

  1. Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, 100084, Beijing, China

    Yi Jiang, Zongrui Luo, Yuanchao Gong, Yan Fu & Yongzhang Luo

  2. The National Engineering Research Center for Protein Technology, Tsinghua University, 100084, Beijing, China

    Yi Jiang, Zongrui Luo, Yuanchao Gong, Yan Fu & Yongzhang Luo

  3. Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, 100084, Beijing, China

    Yi Jiang, Zongrui Luo, Yuanchao Gong, Yan Fu & Yongzhang Luo

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Conceptualization: YJ; Methodology: YJ and YG; Investigation: YJ and ZL; Writing—original draft: YJ; Writing—review and editing: YJ, ZL, YF and YL; Supervision: YL and YF; Funding acquisition: YL and YF.

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Correspondence to Yan Fu or Yongzhang Luo.

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Jiang, Y., Luo, Z., Gong, Y. et al. NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling. Oncogene 42, 808–824 (2023). https://doi.org/10.1038/s41388-023-02592-y

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