Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression

Mika Hilvo, Carsten Denkert, Laura Lehtinen, Berit Müller, Scarlet Brockmöller, Tuulikki Seppänen-Laakso, Jan Budczies, Elmar Bucher, Laxman Yetukuri, Sandra Castillo, Emilia Berg, Heli Nygren, Marko Sysi-Aho, Julian L. Griffin, Oliver Fiehn, Sibylle Loibl, Christiane Richter-Ehrenstein, Cornelia Radke, Tuulia Hyötyläinen, Olli KallioniemiKristiina Iljin, Matej Orešič

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase a), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.

Original languageEnglish (US)
Pages (from-to)3236-3245
Number of pages10
JournalCancer Research
Volume71
Issue number9
DOIs
StatePublished - May 1 2011

Fingerprint

Membrane Lipids
Lipid Metabolism
Breast Neoplasms
Genes
Neoplasms
Lipids
Phospholipids
Proteins
Breast
Fatty Acids
Stearoyl-CoA Desaturase
Sterol Regulatory Element Binding Protein 1
Acetyl-CoA Carboxylase
Fatty Acid Synthases
Palmitates
Gene Silencing
Phosphatidylcholines
Thyroid Hormones
Liquid Chromatography
Estrogen Receptors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hilvo, M., Denkert, C., Lehtinen, L., Müller, B., Brockmöller, S., Seppänen-Laakso, T., ... Orešič, M. (2011). Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. Cancer Research, 71(9), 3236-3245. https://doi.org/10.1158/0008-5472.CAN-10-3894

Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. / Hilvo, Mika; Denkert, Carsten; Lehtinen, Laura; Müller, Berit; Brockmöller, Scarlet; Seppänen-Laakso, Tuulikki; Budczies, Jan; Bucher, Elmar; Yetukuri, Laxman; Castillo, Sandra; Berg, Emilia; Nygren, Heli; Sysi-Aho, Marko; Griffin, Julian L.; Fiehn, Oliver; Loibl, Sibylle; Richter-Ehrenstein, Christiane; Radke, Cornelia; Hyötyläinen, Tuulia; Kallioniemi, Olli; Iljin, Kristiina; Orešič, Matej.

In: Cancer Research, Vol. 71, No. 9, 01.05.2011, p. 3236-3245.

Research output: Contribution to journalArticle

Hilvo, M, Denkert, C, Lehtinen, L, Müller, B, Brockmöller, S, Seppänen-Laakso, T, Budczies, J, Bucher, E, Yetukuri, L, Castillo, S, Berg, E, Nygren, H, Sysi-Aho, M, Griffin, JL, Fiehn, O, Loibl, S, Richter-Ehrenstein, C, Radke, C, Hyötyläinen, T, Kallioniemi, O, Iljin, K & Orešič, M 2011, 'Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression', Cancer Research, vol. 71, no. 9, pp. 3236-3245. https://doi.org/10.1158/0008-5472.CAN-10-3894
Hilvo, Mika ; Denkert, Carsten ; Lehtinen, Laura ; Müller, Berit ; Brockmöller, Scarlet ; Seppänen-Laakso, Tuulikki ; Budczies, Jan ; Bucher, Elmar ; Yetukuri, Laxman ; Castillo, Sandra ; Berg, Emilia ; Nygren, Heli ; Sysi-Aho, Marko ; Griffin, Julian L. ; Fiehn, Oliver ; Loibl, Sibylle ; Richter-Ehrenstein, Christiane ; Radke, Cornelia ; Hyötyläinen, Tuulia ; Kallioniemi, Olli ; Iljin, Kristiina ; Orešič, Matej. / Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. In: Cancer Research. 2011 ; Vol. 71, No. 9. pp. 3236-3245.
@article{5ab4302e4fd645a3967bfe70ac895d7f,
title = "Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression",
abstract = "Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase a), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.",
author = "Mika Hilvo and Carsten Denkert and Laura Lehtinen and Berit M{\"u}ller and Scarlet Brockm{\"o}ller and Tuulikki Sepp{\"a}nen-Laakso and Jan Budczies and Elmar Bucher and Laxman Yetukuri and Sandra Castillo and Emilia Berg and Heli Nygren and Marko Sysi-Aho and Griffin, {Julian L.} and Oliver Fiehn and Sibylle Loibl and Christiane Richter-Ehrenstein and Cornelia Radke and Tuulia Hy{\"o}tyl{\"a}inen and Olli Kallioniemi and Kristiina Iljin and Matej Orešič",
year = "2011",
month = "5",
day = "1",
doi = "10.1158/0008-5472.CAN-10-3894",
language = "English (US)",
volume = "71",
pages = "3236--3245",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression

AU - Hilvo, Mika

AU - Denkert, Carsten

AU - Lehtinen, Laura

AU - Müller, Berit

AU - Brockmöller, Scarlet

AU - Seppänen-Laakso, Tuulikki

AU - Budczies, Jan

AU - Bucher, Elmar

AU - Yetukuri, Laxman

AU - Castillo, Sandra

AU - Berg, Emilia

AU - Nygren, Heli

AU - Sysi-Aho, Marko

AU - Griffin, Julian L.

AU - Fiehn, Oliver

AU - Loibl, Sibylle

AU - Richter-Ehrenstein, Christiane

AU - Radke, Cornelia

AU - Hyötyläinen, Tuulia

AU - Kallioniemi, Olli

AU - Iljin, Kristiina

AU - Orešič, Matej

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase a), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.

AB - Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase a), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.

UR - http://www.scopus.com/inward/record.url?scp=79955518028&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955518028&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-3894

DO - 10.1158/0008-5472.CAN-10-3894

M3 - Article

C2 - 21415164

AN - SCOPUS:79955518028

VL - 71

SP - 3236

EP - 3245

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 9

ER -