Unregulated LDL cholesterol uptake is detrimental to breast cancer cells

in Endocrine-Related Cancer
Authors:
Tiffany Scully Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Abora Ettela Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Nathan Kase Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Derek LeRoith Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Emily Jane Gallagher Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Correspondence should be addressed to E J Gallagher: Emily.Gallagher@mssm.edu
DOI:
https://doi.org/10.1530/ERC-22-0234
Volume/Issue:
Volume 30: Issue 1
Article Type:
Research Article
Article ID:
e220234
Online Publication Date:
12 Dec 2022
Copyright:
© the author(s) 2022
Restricted access
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Tumor uptake of exogenous cholesterol has been associated with the proliferation of various cancers. Previously, we and others have shown that hypercholesterolemia promotes tumor growth and silencing of the LDL receptor (LDLR) in high LDLR-expressing tumors reduces growth. To advance understanding of how LDL uptake promotes tumor growth, LDLR expression was amplified in breast cancer cell lines with endogenously low LDLR expression. Murine (Mvt1) and human (MDA-MB-468) breast cancer cell lines were transduced to overexpress human LDLR (LDLROE). Successful transduction was confirmed by RNA and protein analysis. Fluorescence-labeled LDL uptake was increased in both Mvt1 and MDA-MD-468 LDLROE cells. The expression of the cholesterol-metabolizing genes, ABCA1 and ABCG1, was increased, while HMGCR was decreased in the MDA-MB-468 LDLROE cells. In contrast, Mvt1 LDLROE cells showed no differences in Abca1 and Abcg1 expression and increased Hmgcr expression. Using a Seahorse analyzer, Mvt1 LDLROE cells showed increased respiration (ATP-linked and maximal) relative to controls, while no statistically significant changes in respiration in MDA-MB-468 LDLROE cells were observed. Growth of LDLROE cells was reduced in culture and in hypercholesterolemic mice by two-fold. However, the expression of proliferation-associated markers (Ki67, PCNA and BrdU-label incorporation) was not decreased in the Mvt1 LDLROE tumors and cells. Caspase-3 cleavage, which is associated with apoptosis, was increased in both the Mvt1 and MDA-MB-468 LDLROE cells relative to controls, with the Mvt1 LDLROE cells also showing decreased phosphorylation of p44/42MAPK. Taken together, our work suggests that while additional LDL can promote tumor growth, unregulated and prolonged LDL uptake is detrimental.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2022
Article ID:
e220234
Received Date:
17 Sep 2022
Accepted Date:
18 Oct 2022
Print Publication Date:
01 Jan 2023
Online Publication Date:
12 Dec 2022
Keywords:
LDL receptor; breast cancer; cholesterol; hypercholesterolemia; cholesterol and cancer

  • Alikhani N, Ferguson RD, Novosyadlyy R, Gallagher EJ, Scheinman EJ, Yakar S & Leroith D 2013 Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic mouse model. Oncogene 32 961–967. (https://doi.org/10.1038/onc.2012.113)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Beckwitt CH, Clark AM, Ma B, Whaley D, Oltvai ZN & Wells A 2018 Statins attenuate outgrowth of breast cancer metastases. British Journal of Cancer 119 1094–1105. (https://doi.org/10.1038/s41416-018-0267-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bjarnadottir O, Romero Q, Bendahl PO, Jirström K, Rydén L, Loman N, Uhlén M, Johannesson H, Rose C, Grabau D, et al.2013 Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial. Breast Cancer Research and Treatment 138 499–508. (https://doi.org/10.1007/s10549-013-2473-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cai D, Wang J, Gao B, Li J, Wu F, Zou JX, Xu J, Jiang Y, Zou H, Huang Z, et al.2019 RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype. Nature Communications 10 4621. (https://doi.org/10.1038/s41467-019-12529-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, Guertin DA, Chang JH, Lindquist RA, Moffat J, et al.2006 CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biology 7 R100. (https://doi.org/10.1186/gb-2006-7-10-r100)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chacko BK, Kramer PA, Ravi S, Benavides GA, Mitchell T, Dranka BP, Ferrick D, Singal AK, Ballinger SW, Bailey SM, et al.2014 The Bioenergetic Health Index: a new concept in mitochondrial translational research. Clinical Science 127 367–373. (https://doi.org/10.1042/CS20140101)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dansky HM, Charlton SA, Sikes JL, Heath SC, Simantov R, Levin LF, Shu P, Moore KJ, Breslow JL & Smith JD 1999 Genetic background determines the extent of atherosclerosis in ApoE-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 19 1960–1968. (https://doi.org/10.1161/01.atv.19.8.1960)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • de Gonzalo-Calvo D, López-Vilaró L, Nasarre L, Perez-Olabarria M, Vázquez T, Escuin D, Badimon L, Barnadas A, Lerma E & Llorente-Cortés V 2015 Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study. BMC Cancer 15 460. (https://doi.org/10.1186/s12885-015-1469-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ehmsen S, Pedersen MH, Wang G, Terp MG, Arslanagic A, Hood BL, Conrads TP, Leth-Larsen R & Ditzel HJ 2019 Increased cholesterol biosynthesis is a key characteristic of breast cancer stem cells influencing patient outcome. Cell Reports 27 3927–3938.e6. (https://doi.org/10.1016/j.celrep.2019.05.104)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Feldt M, Menard J, Rosendahl AH, Lettiero B, Bendahl PO, Belting M & Borgquist S 2020 The effect of statin treatment on intratumoral cholesterol levels and LDL receptor expression: a window-of-opportunity breast cancer trial. Cancer and Metabolism 8 25. (https://doi.org/10.1186/s40170-020-00231-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, et al.2003 The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nature Cell Biology 5 781–792. (https://doi.org/10.1038/ncb1035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ferguson RD, Novosyadlyy R, Fierz Y, Alikhani N, Sun H, Yakar S & Leroith D 2012 Hyperinsulinemia enhances c-Myc-mediated mammary tumor development and advances metastatic progression to the lung in a mouse model of type 2 diabetes. Breast Cancer Research 14 R8. (https://doi.org/10.1186/bcr3089)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Freed-Pastor WA, Mizuno H, Zhao X, Langerød A, Moon SH, Rodriguez-Barrueco R, Barsotti A, Chicas A, Li W, Polotskaia A, et al.2012 Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell 148 244–258. (https://doi.org/10.1016/j.cell.2011.12.017)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gallagher EJ, Zelenko Z, Neel BA, Antoniou IM, Rajan L, Kase N & Leroith D 2017 Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia. Oncogene 36 6462–6471. (https://doi.org/10.1038/onc.2017.247)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Göbel A, Breining D, Rauner M, Hofbauer LC & Rachner TD 2019 Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells. Cell Death and Disease 10 91. (https://doi.org/10.1038/s41419-019-1322-x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Goetzman ES & Prochownik EV 2018 The role for myc in coordinating glycolysis, oxidative phosphorylation, glutaminolysis, and fatty acid metabolism in normal and neoplastic tissues. Frontiers in Endocrinology 9 129. (https://doi.org/10.3389/fendo.2018.00129)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guillaumond F, Bidaut G, Ouaissi M, Servais S, Gouirand V, Olivares O, Lac S, Borge L, Roques J, Gayet O, et al.2015 Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. PNAS 112 2473–2478. (https://doi.org/10.1073/pnas.1421601112)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hall Z, Wilson CH, Burkhart DL, Ashmore T, Evan GI & Griffin JL 2020 Myc linked to dysregulation of cholesterol transport and storage in nonsmall cell lung cancer. Journal of Lipid Research 61 1390–1399. (https://doi.org/10.1194/jlr.RA120000899)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hsieh AL, Walton ZE, Altman BJ, Stine ZE & Dang CV 2015 MYC and metabolism on the path to cancer. Seminars in Cell and Developmental Biology 43 11–21. (https://doi.org/10.1016/j.semcdb.2015.08.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang B, Song BL & Xu C 2020 Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities. Nature Metabolism 2 132–141. (https://doi.org/10.1038/s42255-020-0174-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Inasu M, Feldt M, Jernström H, Borgquist S & Harborg S 2022 Statin use and patterns of breast cancer recurrence in the Malmö Diet and Cancer Study. Breast 61 123–128. (https://doi.org/10.1016/j.breast.2022.01.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jeong HJ, Lee HS, Kim KS, Kim YK, Yoon D & Park SW 2008 Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. Journal of Lipid Research 49 399–409. (https://doi.org/10.1194/jlr.M700443-JLR200)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Johnson KE, Siewert KM, Klarin D & Damrauer SM VA Million Veteran Program, Chang KM, Tsao PS, Assimes TL, Maxwell KN & Voight BF 2020 The relationship between circulating lipids and breast cancer risk: a Mendelian randomization study. PLoS Medicine 17 e1003302. (https://doi.org/10.1371/journal.pmed.1003302)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kimbung S, Lettiero B, Feldt M, Bosch A & Borgquist S 2016 High expression of cholesterol biosynthesis genes is associated with resistance to statin treatment and inferior survival in breast cancer. Oncotarget 7 59640–59651. (https://doi.org/10.18632/oncotarget.10746)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kloudova A, Guengerich FP & Soucek P 2017 The role of oxysterols in human cancer. Trends in Endocrinology and Metabolism 28 485–496. (https://doi.org/10.1016/j.tem.2017.03.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lettiero B, Inasu M, Kimbung S & Borgquist S 2018 Insensitivity to atorvastatin is associated with increased accumulation of intracellular lipid droplets and fatty acid metabolism in breast cancer cells. Scientific Reports 8 5462. (https://doi.org/10.1038/s41598-018-23726-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li YR, Ro V, Steel L, Carrigan E, Nguyen J, Williams A, So A & Tchou J 2019 Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer. Breast Cancer Research and Treatment 176 669–677. (https://doi.org/10.1007/s10549-019-05267-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu W, Chakraborty B, Safi R, Kazmin D, Chang CY & Mcdonnell DP 2021 Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nature Communications 12 5103. (https://doi.org/10.1038/s41467-021-25354-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Luchetti G, Sircar R, Kong JH, Nachtergaele S, Sagner A, Byrne EF, Covey DF, Siebold C & Rohatgi R 2016 Cholesterol activates the G-protein coupled receptor smoothened to promote Hedgehog signaling. eLife 5 e20304. (https://doi.org/10.7554/eLife.20304)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Luo J, Yang H & Song BL 2020 Mechanisms and regulation of cholesterol homeostasis. Nature Reviews Molecular Cell Biology 21 225–245. (https://doi.org/10.1038/s41580-019-0190-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Manthravadi S, Shrestha A & Madhusudhana S 2016 Impact of statin use on cancer recurrence and mortality in breast cancer: a systematic review and meta-analysis. International Journal of Cancer 139 1281–1288. (https://doi.org/10.1002/ijc.30185)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nowak C & Ärnlöv J 2018 A Mendelian randomization study of the effects of blood lipids on breast cancer risk. Nature Communications 9 3957. (https://doi.org/10.1038/s41467-018-06467-9)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Papa S, Choy PM & Bubici C 2019 The ERK and JNK pathways in the regulation of metabolic reprogramming. Oncogene 38 2223–2240. (https://doi.org/10.1038/s41388-018-0582-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Parmenter TJ, Kleinschmidt M, Kinross KM, Bond ST, Li J, Kaadige MR, Rao A, Sheppard KE, Hugo W, Pupo GM, et al.2014 Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis. Cancer Discovery 4 423–433. (https://doi.org/10.1158/2159-8290.CD-13-0440)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pei XF, Noble MS, Davoli MA, Rosfjord E, Tilli MT, Furth PA, Russell R, Johnson MD & Dickson RB 2004 Explant-cell culture of primary mammary tumors from MMTV-c-Myc transgenic mice. In Vitro Cellular and Developmental Biology – Animal 40 14–21. (https://doi.org/10.1290/1543-706X(2004)40<14:ECOPMT>2.0.CO;2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pelton K, Coticchia CM, Curatolo AS, Schaffner CP, Zurakowski D, Solomon KR & Moses MA 2014 Hypercholesterolemia induces angiogenesis and accelerates growth of breast tumors in vivo. American Journal of Pathology 184 2099–2110. (https://doi.org/10.1016/j.ajpath.2014.03.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Quiros PM, Goyal A, Jha P & Auwerx J 2017 Analysis of mtDNA/nDNA ratio in mice. Current Protocols in Mouse Biology 7 47–54. (https://doi.org/10.1002/cpmo.21)

  • Radhakrishnan A, Goldstein JL, Mcdonald JG & Brown MS 2008 Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metabolism 8 512–521. (https://doi.org/10.1016/j.cmet.2008.10.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Radhakrishnan A, Rohatgi R & Siebold C 2020 Cholesterol access in cellular membranes controls Hedgehog signaling. Nature Chemical Biology 16 1303–1313. (https://doi.org/10.1038/s41589-020-00678-2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rodrigues Dos Santos C, Fonseca I, Dias S & Mendes de Almeida JC 2014 Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression. BMC Cancer 14 132. (https://doi.org/10.1186/1471-2407-14-132)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Scully T, Kase N, Gallagher EJ & Leroith D 2021 Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling. Scientific Reports 11 17927. (https://doi.org/10.1038/s41598-021-97327-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shen S, Faouzi S, Souquere S, Roy S, Routier E, Libenciuc C, André F, Pierron G, Scoazec JY & Robert C 2020 Melanoma persister cells are tolerant to BRAF/MEK inhibitors via ACOX1-mediated fatty acid oxidation. Cell Reports 33 108421. (https://doi.org/10.1016/j.celrep.2020.108421)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Song Y, Liu J, Zhao K, Gao L & Zhao J 2021 Cholesterol-induced toxicity: an integrated view of the role of cholesterol in multiple diseases. Cell Metabolism 33 1911–1925. (https://doi.org/10.1016/j.cmet.2021.09.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sotgia F, Whitaker-Menezes D, Martinez-Outschoorn UE, Salem AF, Tsirigos A, Lamb R, Sneddon S, Hulit J, Howell A & Lisanti MP 2012 Mitochondria "fuel" breast cancer metabolism: fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells. Cell Cycle 11 4390–4401. (https://doi.org/10.4161/cc.22777)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tabas I 2002 Consequences of cellular cholesterol accumulation: basic concepts and physiological implications. Journal of Clinical Investigation 110 905–911. (https://doi.org/10.1172/JCI16452)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Teupser D, Persky AD & Breslow JL 2003 Induction of atherosclerosis by low-fat, semisynthetic diets in LDL receptor-deficient C57BL/6J and FVB/NJ mice: comparison of lesions of the aortic root, brachiocephalic artery, and whole aorta (en face measurement). Arteriosclerosis, Thrombosis, and Vascular Biology 23 1907–1913. (https://doi.org/10.1161/01.ATV.0000090126.34881.B1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Torres-Adorno AM, Vitrac H, Qi Y, Tan L, Levental KR, Fan YY, Yang P, Chapkin RS, Eckhardt BL & Ueno NT 2019 Eicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux. Oncogene 38 2135–2150. (https://doi.org/10.1038/s41388-018-0569-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Traore K, Sharma R, Thimmulappa RK, Watson WH, Biswal S & Trush MA 2008 Redox-regulation of ERK1/2-directed phosphatase by reactive oxygen species: role in signaling TPA-induced growth arrest in ML-1 cells. Journal of Cellular Physiology 216 276–285. (https://doi.org/10.1002/jcp.21403)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Viswanathan VS, Ryan MJ, Dhruv HD, Gill S, Eichhoff OM, Seashore-Ludlow B, Kaffenberger SD, Eaton JK, Shimada K, Aguirre AJ, et al.2017 Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547 453–457. (https://doi.org/10.1038/nature23007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Voisin M, De Medina P, Mallinger A, Dalenc F, Huc-Claustre E, Leignadier J, Serhan N, Soules R, Ségala G, Mougel A, et al.2017 Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor. PNAS 114 E9346–E9355. (https://doi.org/10.1073/pnas.1707965114)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vona R, Iessi E & Matarrese P 2021 Role of cholesterol and lipid rafts in cancer signaling: a promising therapeutic opportunity? Frontiers in Cell and Developmental Biology 9 622908. (https://doi.org/10.3389/fcell.2021.622908)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang PY, Weng J & Anderson RG 2005 OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science 307 1472–1476. (https://doi.org/10.1126/science.1107710)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Weigelt B, Warne PH & Downward J 2011 PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene 30 3222–3233. (https://doi.org/10.1038/onc.2011.42)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson Ta, Liu X, Ratliff TL, et al.2014 Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metabolism 19 393–406. (https://doi.org/10.1016/j.cmet.2014.01.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang J, Nuebel E, Wisidagama DRR, Setoguchi K, Hong JS, Van Horn CM, Imam SS, Vergnes L, Malone CS, Koehler CM, et al.2012 Measuring energy metabolism in cultured cells, including human pluripotent stem cells and differentiated cells. Nature Protocols 7 1068–1085. (https://doi.org/10.1038/nprot.2012.048)

    • PubMed
    • Search Google Scholar
    • Export Citation