Adrenergic nerves activate an angio-metabolic switch in prostate cancer

Ali H. Zahalka, Anna Arnal-Estapé, Maria Maryanovich, Fumio Nakahara, Cristian D. Cruz, Lydia W.S. Finley, Paul S. Frenette

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial b-adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cellmetabolism. Endothelial cells typically rely on aerobic glycolysis for angiogenesis.We found that the loss of endothelial Adrb2, the gene encoding the b2-adrenergic receptor, leads to inhibition of angiogenesis through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2 and Cox10, a gene encoding a cytochrome IVoxidase assembly factor, prevented the metabolic shift induced by Adrb2 deletion and rescued prostate cancer progression. This cross-talk between nerves and endothelial metabolism could potentially be targeted as an anticancer therapy.

Original languageEnglish (US)
Pages (from-to)321-326
Number of pages6
JournalScience
Volume358
Issue number6361
DOIs
StatePublished - Oct 20 2017

Fingerprint

Adrenergic Agents
Adrenergic Receptors
Prostatic Neoplasms
Tumor Microenvironment
Oxidative Phosphorylation
Glycolysis
Cytochromes
Nerve Fibers
Genes
Blood Vessels
Prostate
Norepinephrine
Endothelial Cells
Growth
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Zahalka, A. H., Arnal-Estapé, A., Maryanovich, M., Nakahara, F., Cruz, C. D., Finley, L. W. S., & Frenette, P. S. (2017). Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science, 358(6361), 321-326. https://doi.org/10.1126/science.aah5072

Adrenergic nerves activate an angio-metabolic switch in prostate cancer. / Zahalka, Ali H.; Arnal-Estapé, Anna; Maryanovich, Maria; Nakahara, Fumio; Cruz, Cristian D.; Finley, Lydia W.S.; Frenette, Paul S.

In: Science, Vol. 358, No. 6361, 20.10.2017, p. 321-326.

Research output: Contribution to journalArticle

Zahalka, AH, Arnal-Estapé, A, Maryanovich, M, Nakahara, F, Cruz, CD, Finley, LWS & Frenette, PS 2017, 'Adrenergic nerves activate an angio-metabolic switch in prostate cancer', Science, vol. 358, no. 6361, pp. 321-326. https://doi.org/10.1126/science.aah5072
Zahalka AH, Arnal-Estapé A, Maryanovich M, Nakahara F, Cruz CD, Finley LWS et al. Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science. 2017 Oct 20;358(6361):321-326. https://doi.org/10.1126/science.aah5072
Zahalka, Ali H. ; Arnal-Estapé, Anna ; Maryanovich, Maria ; Nakahara, Fumio ; Cruz, Cristian D. ; Finley, Lydia W.S. ; Frenette, Paul S. / Adrenergic nerves activate an angio-metabolic switch in prostate cancer. In: Science. 2017 ; Vol. 358, No. 6361. pp. 321-326.
@article{a716ef92b36b48489dffd986127ab698,
title = "Adrenergic nerves activate an angio-metabolic switch in prostate cancer",
abstract = "Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial b-adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cellmetabolism. Endothelial cells typically rely on aerobic glycolysis for angiogenesis.We found that the loss of endothelial Adrb2, the gene encoding the b2-adrenergic receptor, leads to inhibition of angiogenesis through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2 and Cox10, a gene encoding a cytochrome IVoxidase assembly factor, prevented the metabolic shift induced by Adrb2 deletion and rescued prostate cancer progression. This cross-talk between nerves and endothelial metabolism could potentially be targeted as an anticancer therapy.",
author = "Zahalka, {Ali H.} and Anna Arnal-Estap{\'e} and Maria Maryanovich and Fumio Nakahara and Cruz, {Cristian D.} and Finley, {Lydia W.S.} and Frenette, {Paul S.}",
year = "2017",
month = "10",
day = "20",
doi = "10.1126/science.aah5072",
language = "English (US)",
volume = "358",
pages = "321--326",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6361",

}

TY - JOUR

T1 - Adrenergic nerves activate an angio-metabolic switch in prostate cancer

AU - Zahalka, Ali H.

AU - Arnal-Estapé, Anna

AU - Maryanovich, Maria

AU - Nakahara, Fumio

AU - Cruz, Cristian D.

AU - Finley, Lydia W.S.

AU - Frenette, Paul S.

PY - 2017/10/20

Y1 - 2017/10/20

N2 - Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial b-adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cellmetabolism. Endothelial cells typically rely on aerobic glycolysis for angiogenesis.We found that the loss of endothelial Adrb2, the gene encoding the b2-adrenergic receptor, leads to inhibition of angiogenesis through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2 and Cox10, a gene encoding a cytochrome IVoxidase assembly factor, prevented the metabolic shift induced by Adrb2 deletion and rescued prostate cancer progression. This cross-talk between nerves and endothelial metabolism could potentially be targeted as an anticancer therapy.

AB - Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial b-adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cellmetabolism. Endothelial cells typically rely on aerobic glycolysis for angiogenesis.We found that the loss of endothelial Adrb2, the gene encoding the b2-adrenergic receptor, leads to inhibition of angiogenesis through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2 and Cox10, a gene encoding a cytochrome IVoxidase assembly factor, prevented the metabolic shift induced by Adrb2 deletion and rescued prostate cancer progression. This cross-talk between nerves and endothelial metabolism could potentially be targeted as an anticancer therapy.

UR - http://www.scopus.com/inward/record.url?scp=85032504920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032504920&partnerID=8YFLogxK

U2 - 10.1126/science.aah5072

DO - 10.1126/science.aah5072

M3 - Article

C2 - 29051371

AN - SCOPUS:85032504920

VL - 358

SP - 321

EP - 326

JO - Science

JF - Science

SN - 0036-8075

IS - 6361

ER -