Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts

Zhuang, Liyan; Kim, Jayoung; Adam, Rosalyn M.; Solomon, Keith R.; Freeman, Michael R.

doi:10.1172/jci200519935

Cited by 567Cancer, Lipids, and MetabolismCaveolin-1 and cellular processesLipid Membrane Structure and Behavior

Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts

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Zhuang, Liyan, Kim, Jayoung, Adam, Rosalyn M., Solomon, Keith R., Freeman, Michael R.·2005·Journal of Clinical Investigation

DOI 10.1172/jci200519935PMC PMC1064980

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Abstract

Lipid rafts are cholesterol-and sphingolipid-enriched microdomains in cell membranes that regulate phosphorylation cascades originating from membrane-bound proteins.In this study, we tested whether alteration of the cholesterol content of lipid rafts in prostate cancer (PCa) cell membranes affects cell survival mechanisms in vitro and in vivo.Simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, inhibited Akt1 serine-threonine kinase (protein kinase Bα)/protein kinase B (Akt/PKB) pathway signaling, and induced apoptosis in caveolin-and PTEN-negative LNCaP PCa cells.Replenishing cell membranes with cholesterol reversed these inhibitory and apoptotic effects.Cholesterol also potentiated Akt activation in normal prostate epithelial cells, which were resistant to the apoptotic effects of simvastatin.Elevation of circulating cholesterol in SCID mice increased the cholesterol content and the extent of protein tyrosine phosphorylation in lipid rafts isolated from LNCaP/sHB xenograft tumors.Cholesterol elevation also promoted tumor growth, increased phosphorylation of Akt, and reduced apoptosis in the xenografts.Our results implicate membrane cholesterol in Akt signaling in both normal and malignant cells and provide evidence that PCa cells can become dependent on a cholesterol-regulated Akt pathway for cell survival.

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Cholesterol deprivation can inhibit tumor growth, decrease phosphorylation of AKT, promote apoptosis, decrease Bcl-xl, downregulate caspase 3 activation, or hinder entry of cells into S phase.
“cholesterol deprivation can inhibit tumor growth, decrease the phosphorylation of AKT, promote apoptosis62, decrease Bcl-xl, downregulate caspase 3 activation63, or hinder entry of cells into the S phase64.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [62]

1 retracted

Cholesterol Depletion Inhibits Epidermal Growth Factor Receptor Transactivation by Angiotensin II in Vascular Smooth Muscle Cells
Ushio‐Fukai, M., Hilenski, L. L., Santanam, N., Becker, P. L., Ma, Y., Griendling, K. K., & Alexander, R. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105901200 · Cited by 204 · see citing works
Retracted
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
Vivanco, I., & Sawyers, C. L. (2002) · Nature reviews. Cancer · doi:10.1038/nrc839 · Cited by 6,041 · see citing works
Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice
Dráb, M., Verkade, P., Elger, M., Kasper, M. E., Löhn, M., Lauterbach, B., Menne, J., Lindschau, C., Mende, F., Luft, F. C., et al. (2001) · Science · doi:10.1126/science.1062688 · Cited by 1,555 · see citing works
Lipid rafts: bringing order to chaos
PIKE, L. J. (2003) · Journal of Lipid Research · doi:10.1194/jlr.r200021-jlr200 · Cited by 1,139 · see citing works
Role of Translocation in the Activation and Function of Protein Kinase B
Andjelkovic, M., Alessi, D. R., Meier, R., Fernandez, A., Lamb, N. J. C., Frech, M., Cron, P., Cohen, P., Lucocq, J. M., & Hemmings, B. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31515 · Cited by 1,051 · see citing works
Hedgehog signalling in prostate regeneration, neoplasia and metastasis
Karhadkar, S. S., Bova, G. S., Abdallah, N., Dhara, S., Gardner, D. R., Maitra, A., Isaacs, J. T., Berman, D. M., & Beachy, P. A. (2004) · Nature · doi:10.1038/nature02962 · Cited by 950 · see citing works
A Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk
Giovannucci, E. L. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.5.391 · Cited by 877 · see citing works
Src Tyrosine Kinases, Gα Subunits, and H-Ras Share a Common Membrane-anchored Scaffolding Protein, Caveolin
Li, S. C., Couët, J., & Lisanti, M. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.46.29182 · Cited by 778 · see citing works
The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway
Wu, X., Senechal, K., Neshat, M. S., Whang, Y. E., & Sawyers, C. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15587 · Cited by 674 · see citing works
Multiple Functions of Caveolin-1
Liu, P., Rudick, M. J., & Anderson, R. G. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r200020200 · Cited by 591 · see citing works
Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors.
Andjelkovic, M., Jakubowicz, T., Cron, P., Ming, X., Han, J. W., & Hemmings, B. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.12.5699 · Cited by 525 · see citing works
The Risk of Cancer in Users of Statins
Graaf, M. R., Beiderbeck, A. B., Egberts, T. C. G., Richel, D. J., & Guchelaar, H. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.027 · Cited by 524 · see citing works
Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling
Sánchez‐Gómez, P., Hernández, A., Stecca, B. A., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404956101 · Cited by 517 · see citing works
Identification of a PKB/Akt Hydrophobic Motif Ser-473 Kinase as DNA-dependent Protein Kinase
Feng, J., Park, J., Cron, P. D., Heß, D., & Hemmings, B. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406731200 · Cited by 488 · see citing works
Simvastatin Has Anti-Inflammatory and Antiatherosclerotic Activities Independent of Plasma Cholesterol Lowering
Sparrow, C. P., Burton, C. A., Hernandez, M., Mundt, S. S., Hassing, H., Patel, S., Rosa, R., Hermanowski‐Vosatka, A., Wang, P.-R., Zhang, D., et al. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.21.1.115 · Cited by 413 · see citing works
Multiple Phosphoinositide 3-Kinase-Dependent Steps in Activation of Protein Kinase B
Scheid, M. P., Marignani, P. A., & Woodgett, J. R. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.17.6247-6260.2002 · Cited by 328 · see citing works
Identification of a Structural Determinant Necessary for the Localization and Function of Estrogen Receptor α at the Plasma Membrane
Razandi, M., Alton, G., Pedram, A., Ghonshani, S., Webb, P., & Levin, E. R. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.5.1633-1646.2003 · Cited by 319 · see citing works
Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study
Denoyelle, C. (2001) · Carcinogenesis · doi:10.1093/carcin/22.8.1139 · Cited by 317 · see citing works
Caveolae: anchored, multifunctional platforms in the lipid ocean
van Deurs, B., Roepstorff, K., Hommelgaard, A. M., & Sandvig, K. (2003) · Trends in Cell Biology · doi:10.1016/s0962-8924(02)00039-9 · Cited by 296 · see citing works
Caveolin-1 Maintains Activated Akt in Prostate CancerCells through Scaffolding Domain Binding Site Interactions with andInhibition of Serine/Threonine Protein Phosphatases PP1 andPP2A
Li, L., Ren, C. H., Tahir, S. A., Ren, C., & Thompson, T. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9389-9404.2003 · Cited by 291 · see citing works
Hedgehog Signaling Promotes Prostate Xenograft Tumor Growth
Fan, L., Pepicelli, C. V., Dibble, C. C., et al. (2004) · Endocrinology · doi:10.1210/en.2004-0079 · Cited by 286 · see citing works
Caveolin-1 Is Down-Regulated in Human Ovarian Carcinoma and Acts as a Candidate Tumor Suppressor Gene
Wiechen, K., Diatchenko, L. B., Agoulnik, A. I., et al. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63010-6 · Cited by 281 · see citing works
Follow-up study of patients randomized in the scandinavian simvastatin survival study (4S) of cholesterol lowering
Pedersen, T. R., Wilhelmsen, L., Færgeman, O., Strandberg, T. E., Þorgeirsson, G., Troedsson, L., Kristianson, J., Berg, K., Cook, T. J., Haghfelt, T. H., et al. (2000) · The American Journal of Cardiology · doi:10.1016/s0002-9149(00)00910-3 · Cited by 273 · see citing works
The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice
Joyce, C. W., Amar, M. J., Lambert, G. C., Vaisman, B. L., Paigen, B. J., Najib-Fruchart, J., Hoyt, R. F., Neufeld, E. D., Remaley, A. T., Fredrickson, D. S., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012587699 · Cited by 269 · see citing works
Cholesterol and prostate cancer
Freeman, M. R., & Solomon, K. R. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10724 · Cited by 268 · see citing works
Self-citation
Role of PI3K Signaling in Survival and Progression of LNCaP Prostate Cancer Cells to the Androgen Refractory State
Murillo, H., Huang, H., Schmidt, L. J., Smith, D. I., & Tindall, D. J. (2001) · Endocrinology · doi:10.1210/endo.142.11.8467 · Cited by 263 · see citing works
Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype
Park, D. S., Woodman, S. E., Schubert, W., Cohen, A. W., Frank, P. G., Chandra, M., Shirani, J., Razani, B., Tang, B., Jelicks, L. A., et al. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61168-6 · Cited by 251 · see citing works
Phosphoinositides and phosphoinositide-utilizing enzymes in detergent-insoluble lipid domains.
Hope, H. R., & PIKE, L. J. (1996) · Molecular Biology of the Cell · doi:10.1091/mbc.7.6.843 · Cited by 241 · see citing works
Caveolin-1 Interacts with Androgen Receptor
Lu, M. L., Schneider, M. C., Zheng, Y., Zhang, X., & Richie, J. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006598200 · Cited by 239 · see citing works
Overexpression of caveolin‐1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage
Kato, K., Hida, Y., Miyamoto, M., et al. (2002) · Cancer · doi:10.1002/cncr.10329 · Cited by 236 · see citing works
Similarities of prostate and breast cancer: Evolution, diet, and estrogens
Coffey, D. S. (2001) · Urology · doi:10.1016/s0090-4295(00)00938-9 · Cited by 228 · see citing works
A prospective study on intake of animal products and risk of prostate cancer
Michaud, D. S., Bälter, K. A., Rimm, E. B., Stampfer, M. J., Willett, W. C., & Giovannucci, E. L. (2001) · Cancer Causes & Control · doi:10.1023/a:1011256201044 · Cited by 218 · see citing works
Reciprocal Regulation of Neu Tyrosine Kinase Activity and Caveolin-1 Protein Expression in Vitro and in Vivo
Engelman, J. A., Lee, R. J., Karnezis, A. N., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20448 · Cited by 211 · see citing works
Cytokine Signaling
Sehgal, P. B., Guo, G. G., Shah, M., Kumar, V., & Patel, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200018200 · Cited by 184 · see citing works
Identification of a Plasma Membrane Raft-Associated PKB Ser473 Kinase Activity that Is Distinct from ILK and PDK1
Hill, M. M. C., Feng, J., & Hemmings, B. A. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00973-9 · Cited by 172 · see citing works
Low-Density Lipoprotein Receptor Family
Bu, G., Li, Y., & Cam, J. A. (2001) · Molecular Neurobiology · doi:10.1385/mn:23:1:53 · Cited by 157 · see citing works
The Sonic Hedgehog Receptor Patched Associates with Caveolin-1 in Cholesterol-rich Microdomains of the Plasma Membrane
Karpen, H. E., Bukowski, J. T., Hughes, T. E., Gratton, J., Sessa, W. C., & Gailani, M. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010832200 · Cited by 144 · see citing works
Simvastatin Promotes Atherosclerotic Plaque Stability in ApoE-Deficient Mice Independently of Lipid Lowering
Bea, F., Blessing, E., Bennett, B. J., Levitz, M., Wallace, E. P., & Rosenfeld, M. E. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000036081.01231.16 · Cited by 144 · see citing works
Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma
Suzuoki, M., Miyamoto, M., Kato, K., Hiraoka, K., Oshikiri, T., Nakakubo, Y., Fukunaga, A., Shichinohe, T., Shinohara, T., Itoh, T., et al. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600619 · Cited by 142 · see citing works
Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice
Williams, T. M., Cheung, M. W.-C., Park, D. S., Razani, B., Cohen, A. W., Muller, W. J., Vizio, D. D., Chopra, N. G., Pestell, R. G., & Lisanti, M. P. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-08-0503 · Cited by 138 · see citing works
Molecular mechanism of the anti-cancer activity of cerivastatin, an inhibitor of HMG-CoA reductase, on aggressive human breast cancer cells
Denoyelle, C., Albanese, P., Uzan, G., Li, H., Vannier, J., Soria, J., & Soria, C. (2003) · Cellular Signalling · doi:10.1016/s0898-6568(02)00124-9 · Cited by 120 · see citing works
Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)
Ngo, T. H., Barnard, R. J., Tymchuk, C. N., et al. (2002) · Cancer Causes & Control · doi:10.1023/a:1021911517010 · Cited by 120 · see citing works
Direct Identification of Tyrosine 474 as a Regulatory Phosphorylation Site for the Akt Protein Kinase
Conus, N. M., Hannan, K. M., Cristiano, B. E., Hemmings, B. A., & Pearson, R. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203387200 · Cited by 114 · see citing works
Statin use, hyperlipidaemia, and the risk of breast cancer
Kaye, J. A., Meier, C. R., Walker, A. M., & Jick, H. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600267 · Cited by 87 · see citing works
Simvastatin Reduces Neointimal Thickening in Low-Density Lipoprotein Receptor–Deficient Mice After Experimental Angioplasty Without Changing Plasma Lipids
Chen, Z., Fukutomi, T., Zago, A. C., Ehlers, R., Detmers, P. A., Wright, S. D., Rogers, C., & Simon, D. I. (2002) · Circulation · doi:10.1161/01.cir.0000022843.76104.01 · Cited by 85 · see citing works
Inhibition of orthotopic growth and metastasis of androgen‐sensitive human prostate tumors in mice by bioactive soybean components
Zhou, J., Yu, L., Zhong, Y., Nassr, R. L., Franke, A. A., Gaston, S. M., & Blackburn, G. L. (2002) · The Prostate · doi:10.1002/pros.10141 · Cited by 84 · see citing works
Determination of the non-ionic detergent insolubility and phosphoprotein associations of glycosylphosphatidylinositol-anchored proteins expressed on T cells
Solomon, K. R., Mallory, M. A., & Finberg, R. W. (1998) · Biochemical Journal · doi:10.1042/bj3340325 · Cited by 75 · see citing works
Self-citation
Sterol‐independent regulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase in tumor cells
Hentosh, P., Yuh, S. H., Elson, C. E., et al. (2001) · Molecular Carcinogenesis · doi:10.1002/mc.1074 · Cited by 75 · see citing works
Involvement of Cholesterol-Rich Lipid Rafts in Interleukin-6-Induced Neuroendocrine Differentiation of LNCaP Prostate Cancer Cells
Kim, J., Adam, R. M., Solomon, K. R., et al. (2003) · Endocrinology · doi:10.1210/en.2003-0772 · Cited by 73 · see citing works
Self-citation
Heparin-Binding Epidermal Growth Factor-Like Growth Factor Stimulates Androgen-Independent Prostate Tumor Growth and Antagonizes Androgen Receptor Function
Adam, R. M., Kim, J., Lin, J., Anna Orsola, A., Zhuang, L., Rice, D. C., & Freeman, M. R. (2002) · Endocrinology · doi:10.1210/en.2002-220561 · Cited by 56 · see citing works
Self-citation
Association of energy intake with prostate cancer in a long-term aging study: Baltimore longitudinal study of aging (United States)
Hsieh, L., Carter, H. B., Landis, P., Tucker, K. L., Metter, E. J., Newschaffer, C. J., & Platz, E. A. (2003) · Urology · doi:10.1016/s0090-4295(02)02120-9 · Cited by 46 · see citing works
Caveolae in Human and Murine Osteoblasts
Solomon, K. R., Adolphson, L. D., Wank, D. A., et al. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.12.2391 · Cited by 33 · see citing works
Self-citation
Effects of Simvastatin on Plasma Lipoproteins and Response to Arterial Injury in Wild-Type and Apolipoprotein-E-Deficient Mice
Choudhury, R. P., Carrelli, A. L., Stern, J. D., et al. (2004) · Journal of Vascular Research · doi:10.1159/000076436 · Cited by 32 · see citing works
Pharmacology and clinical experience with simvastatin
Hess, D. C., & Fagan, S. C. (2001) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2.1.153 · Cited by 26 · see citing works
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Zhu, M.-L., & Kyprianou, N. (2008) · Endocrine Related Cancer · doi:10.1677/erc-08-0084 · Cited by 286 · see citing works
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Authors: Zhuang, L., Kim, J., Adam, R. M., Solomon, K. R., & Freeman, M. R.
Affiliations: Boston Children's Hospital (US)
Corresponding author: Freeman, Michael R.
ORCID: Adam, Rosalyn M.
Solomon, Keith R.
Freeman, Michael R.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-03-17
Volume: 115
Issue: 4
Pages: 959-968
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200519935
PMC: PMC1064980
OpenAlex: W4233116228
Cited by: 567
References: 55
Citations by year: 2026: 5 · 2025: 20 · 2024: 19 · 2023: 29 · 2022: 17 · 2021: 37 · 2020: 23 · 2019: 41 · 2018: 27 · 2017: 27 · 2016: 24 · 2015: 23 · 2014: 30 · 2013: 28 · 2012: 34
FWCI: 9.65
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Defense
National Institutes of Health
National Cancer Institute (R01CA101046)
National Institute of Diabetes and Digestive and Kidney Diseases (R37 DK47556, P50DK65298, R37DK047556, P50DK065298)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords: cholesterol, lipid rafts, prostate cancer, simvastatin, Akt signaling, apoptosis, cell survival, LNCaP cells, tumor xenografts, tyrosine phosphorylation, tumor growth, circulating cholesterol
MeSH terms: Animals, Anticholesteremic Agents, Cell Survival, Cholesterol, Enzyme Activation, Humans, Male, Phosphorylation, Prostatic Neoplasms, Proto-Oncogene Proteins, Transplantation, Heterologous, Signal Transduction, Mice, SCID, Apoptosis, Protein Serine-Threonine Kinases, Simvastatin, Membrane Microdomains, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, Mice

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Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts

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