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Advances in Analyzing the Breast Cancer Lipidome and Its Relevance to Disease Progression and Treatment

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Abstract

Abnormal lipid metabolism is common in breast cancer with the three main subtypes, hormone receptor (HR) positive, human epidermal growth factor 2 (HER2) positive, and triple negative, showing common and distinct lipid dependencies. A growing body of studies identify altered lipid metabolism as impacting breast cancer cell growth and survival, plasticity, drug resistance, and metastasis. Lipids are a class of nonpolar or polar (amphipathic) biomolecules that can be produced in cells via de novo synthesis or acquired from the microenvironment. The three main functions of cellular lipids are as essential components of membranes, signaling molecules, and nutrient storage. The use of mass spectrometry-based lipidomics to analyze the global cellular lipidome has become more prevalent in breast cancer research. In this review, we discuss current lipidomic methodologies, highlight recent breast cancer lipidomic studies and how these findings connect to disease progression and therapeutic development, and the potential use of lipidomics as a diagnostic tool in breast cancer. A better understanding of the breast cancer lipidome and how it changes during drug resistance and tumor progression will allow informed development of diagnostics and novel targeted therapies.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

APCI:

Atmospheric pressure chemical ionization

APPI:

Atmospheric pressure polarization ionization

BmP:

Bis(monoacylglycero)phosphate

BUME:

Butanol/methanol

Cer:

Ceramide

ChEBI:

Chemical entities of biological interest

CL:

Cardiolipin

CPT1:

Carnitine palmitoyltransferase I

DESI:

Desorption electrospray ionization

DG:

Diacylglycerol

ER:

Estrogen receptor

ESI:

Electron spray ionization

FA:

Fatty acid

FAO:

Fatty acid oxidation

FASN:

Fatty acid synthase

GC-MS:

Gas chromatography mass spectrometry

GlcCer:

Glucosylceramide

HER2 + :

Human epidermal growth factor receptor 2-positive

HexCer:

Hexosylceramide

HMBD:

Human metabolome data base

HR:

Hormone receptor

LacCer:

Lactosylceramide

LION:

Lipid Ontology Enrichment Analysis

LIPEA:

Lipid Pathway Enrichment Analysis

LPC:

Lysophosphatidylcholine

MALDI:

Matrix assisted laser desorption/ionization

Met:

Methionine

MRI:

Magnetic resonance imaging

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

MTBE:

Methyl tert-butyl ether

MUFA:

Monounsaturated fatty acid

NMR:

Nuclear magnetic resonance

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PI:

Phosphatidylinositol

PI3K:

Phosphoinositide 3-kinase

PIP2:

Phosphatidylinositol (4,5)-trisphosphate

PIP3:

Phosphatidylinositol (3,4,5)-trisphosphate

PKC:

Protein kinase C

PLIN:

Perilipin

PR:

Progesterone receptor

PS:

Phosphatidylserine

PUFA:

Poly unsaturated fatty acid

SCD:

Stearoyl-CoA desaturase

SIMS:

Secondary ion mass spectrometry

SM:

Sphingomyelin

SREBP:

Sterol regulatory element-binding protein

SSO:

Sulfosuccinimidyl oleate

TCA:

Tricarboxylic acid

TG:

Triacylglycerol

TNBC:

Triple negative breast cancer

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Funding

This work was funded in part by the National Institute of Health [R01CA140985 and R01CA229697(CAS)] and Breast Cancer Research Foundation [19–144 (CAS)]. AVW was supported by the National Institutes of Health (F31 CA261053, T32 CA190216, and linked award TL1 TR002533). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health foundation for the national institutes of health, R01CA140985, Carol A Sartorius, F31CA261053, Ashley V. Ward, T32CA190216, Ashley V. Ward, breast cancer research foundation, 19–144, Carol A Sartorius, cancer league of colorado, TL1TR002533, Ashley V. Ward

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  1. Cancer Biology Graduate Program, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

    Ashley V. Ward

  2. Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

    Ashley V. Ward, Steven M. Anderson & Carol A. Sartorius

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Ashley Ward – conception, review of the literature, draft preparation, editing. Steven Anderson – conception, editing. Carol Sartorius – conception, editing.

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Correspondence to Carol A. Sartorius.

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Ward, A.V., Anderson, S.M. & Sartorius, C.A. Advances in Analyzing the Breast Cancer Lipidome and Its Relevance to Disease Progression and Treatment. J Mammary Gland Biol Neoplasia 26, 399–417 (2021). https://doi.org/10.1007/s10911-021-09505-3

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