Neoplasma Vol.67, No.5, p.947–957, 2020
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| Title: Norepinephrine release may play a critical role in the Warburg effect: an integrative model of tumorigenesis |
| Author: P. J. Fitzgerald |
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Abstract: Many cancer cells share the property of carrying out markedly elevated rates of glycolysis to generate energy even in the presence of sufficient oxygen, and this is known as the Warburg effect. In recent years, there has been a resurgence of interest in the Warburg effect, as the field of oncology has amassed evidence that cellular metabolism may play a prominent role in many neoplasms. Largely in the past decade, another prominent and perhaps surprising factor has emerged in the cancer literature: the catecholamine molecules, epinephrine (adrenaline) and norepinephrine (noradrenaline), appear to play a role in tumorigenesis and metastasis. The drug propranolol, which blocks beta-adrenergic receptors, may be therapeutic in human angiosarcoma, melanoma, and ovarian cancer. The current paper synthesizes these older and more recent findings, in an attempt to unify the major factors that contribute to tumorigenesis. This paper suggests that in addition to the direct interaction of catecholamine signaling with genetic risk factors (including mutagenesis), it interacts with environmental factors such as hypertension, obesity, unhealthy dietary components, physical inactivity, substance abuse, and mental or emotional stress, to promote the Warburg effect by facilitating glucose availability through suppression of pancreatic insulin release. Further, it proposes that many cancer cells synthesize and release catecholamines to activate their own receptors in an autocrine fashion. In summary, catecholamines are an important “new” factor in cancer that may interface with both genetics and environmental factors to alter the Warburg effect and modulate tumorigenesis.
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| Keywords: beta-blocker, microenvironment, prazosin, pancreas, clonidine, guanfacine, genetics |
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Published online: 25-May-2020
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| Year: 2020, Volume: 67, Issue: 5 |
Page From: 947, Page To: 957 |
doi:10.4149/neo_2020_200422N432
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