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Targeting Metabolic Cross Talk between Cancer Cells and Cancer-Associated Fibroblasts

  • Jin G. Jung
  • Anne Le
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1063)

Abstract

Although tumorigenesis has classically been regarded as a genetic disease of uncontrolled cell growth, the importance of the tumor microenvironment (TME) is continuously emphasized by the accumulating evidence that cancer growth is not simply dependent on the cancer cells themselves [1, 2] but also dependent on angiogenesis [3–6], inflammation [7, 8], and the supporting roles of cancer-associated fibroblasts (CAFs) [9, 10]. After the discovery that CAFs are able to remodel the tumor matrix within the TME and provide the nutrients and chemicals to promote cancer cell growth [11], many studies have aimed to uncover the cross talk between cancer and CAFs. Moreover, a new paradigm in cancer metabolism shows how cancer cells act like “metabolic parasites” to uptake the high-energy metabolites, such as lactate, ketone bodies, free fatty acid, and glutamine from supporting cells, including CAFs and cancer-associated adipocytes (CAAs) [12, 13]. This chapter provides an overview of the metabolic coupling between CAFs and cancer to further define the therapeutic options to disrupt the CAF-cancer cell interactions.

Keywords

Cancer-associated fibroblasts Cancer-associated adipocytes Tumor microenvironment Metabolism Metabolites Cancer therapy 

Abbreviations

βOHB

β-Hydroxybutyrate

ACAT1

Acetyl-CoA acetyltransferase

ACC

Acetyl-CoA carboxylase

ACCA

Alpha-cyano-4-hydroxycinnamic acid

ACLY

ATP citrate lyase

ASCT2

Alanine, serine, cysteine-preferring transporter 2

BDH1

3-Hydroxybutyrate dehydrogenase 1

CAAs

Cancer-associated adipocytes

CAFs

Cancer-associated fibroblasts

DAG

Diacylglycerol

ECM

Extracellular matrix

EGF

Epidermal growth factor

FASN

Fatty acid synthase

G3P

Glycerol-3-phosphate

GLS

Glutaminase

HGH

Human growth hormone

HMG-CoA

3-Hydroxy-3-methylglutaryl-CoA

HMGCS2

3-Hydroxy-3-methylglutaryl-CoA synthase 2

HSP60

Heat-shock protein 60

LPA

Lysophosphatidic acid

MCT1

Monocarboxylate transporter 1

MCT4

Monocarboxylate transporter 4

MMP

Matrix metalloprotease

OXPHOS

Oxidative phosphorylation

PA

Phosphatidic acid

PI3K

Phosphoinositide 3-kinase

PIP3

Phosphatidylinositol (3,4,5)-trisphosphate

PTEN

Phosphatase and tensin homolog deleted on chromosome 10

TAG

Triacylglycerol

TCA

Tricarboxylic acid

TME

Tumor microenvironment

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Pathology and OncologyJohns Hopkins University School of MedicineBaltimoreUSA

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