Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis. (15th February 2018)

• Record Type: Journal Article
• Authors: Saavedra-García, Paula; Nichols, Katie; Mahmud, Zimam; Fan, Lavender Yuen-Nam; Lam, Eric W-F.
• Is Part Of: Molecular and cellular endocrinology. Volume 462:Part B(2018)
• Page Start: 82
• Page End: 92
• Publication Date: 2018-02-15
• Subjects: Fatty acids -- Cancer -- Lipid metabolism -- FOXO3 -- FOXM1 -- AKT/PI3K pathway; AKT protein kinase B -- AMPK adenosine monophosphate-activated-activated protein kinase -- APN adiponectin -- CoA coenzyme A -- CPT1 carnitine palmitoyltransferase 1 -- DHA docosahexaenoic acid -- EPA eicosapentaenoic acid -- ER endoplasmic reticulum -- ERK extracellular signal-related kinase -- FA fatty acid -- FABP fatty acid-binding protein -- FASN fatty acid synthase -- FFA free fatty acid -- FOX forkhead box -- IGF-I insulin-like growth factor 1 -- IL interleukin -- LCFA long-chain fatty acids -- MAPK mitogen-activated protein kinase -- MUFA monounsaturated fatty acid -- PI3K phosphoinositide 3-kinase -- PPAR peroxisome proliferator-activated receptor -- PUFA polyunsaturated fatty acid -- SFA saturated fatty acid -- TAG triacylglycerol -- TNF-α tumour necrosis factor alpha; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.01.012
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Obesity and cachexia represent divergent states of nutritional and metabolic imbalance but both are intimately linked to cancer. There is an extensive overlap in their signalling pathways and molecular components involved such as fatty acids (FAs), which likely play a crucial role in cancer. Forkhead box (FOX) proteins are responsible of a wide range of transcriptional programmes during normal development, and the FOXO3-FOXM1 axis is associated with cancer initiation, progression and drug resistance. Free fatty acids (FFAs), FA synthesis and β-oxidation are associated with cancer development and progression. Meanwhile, insulin and some adipokines, that are up-regulated by FAs, are also involved in cancer development and poor prognosis. In this review, we discuss the role of FA metabolism in cancer and how FA metabolism integrates with the FOXO3-FOXM1 axis. These new insights may provide leads to better cancer diagnostics as well as strategies for tackling cancer development, progression and drug resistance. Highlights: Fatty acids (FAs) play a crucial role in cancer. The FOXO3-FOXM1 axis promotes cancer initiation, progression and drug resistance. FFA, FASN and β-oxidation are associated with cancer development and progression through the FOXO3-FOXM1 axis. Insulin and some adipokines are related with cancer development and poor prognosis. The link between FOXO3-FOXM1 axis and FA metabolism could be targeted to improve cancer prevention, diagnosis and treatment.