New Insight on Solute Carrier Family 27 Member 6 (SLC27A6) in Tumoral and Non-Tumoral Breast Cells

Yen, Meng‐Chi; Chou, Shih-Kai; Kan, Jung‐Yu; Kuo, Po‐Lin; Hou, Ming‐Feng; Hsu, Ya‐Ling

doi:10.7150/ijms.29946

Cited by 21 publications

(26 citation statements)

References 38 publications

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“…SLC27 consists of a family of six members, from SLC27A1 through SLC27A6, for the uptake of long chain fatty acids. Each family member displays specific substrate and tissue distribution, and the expression of SLC27 family members is associated with tumor fatty acid uptake [ 50 , 51 , 52 , 53 ]. FABPs are a group of low molecular weight proteins (14–15 kda) comprising 12 family members.…”

Section: Fasn and Cancermentioning

confidence: 99%

Fatty Acid Synthase: An Emerging Target in Cancer

2020

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In recent years, lipid metabolism has garnered significant attention as it provides the necessary building blocks required to sustain tumor growth and serves as an alternative fuel source for ATP generation. Fatty acid synthase (FASN) functions as a central regulator of lipid metabolism and plays a critical role in the growth and survival of tumors with lipogenic phenotypes. Accumulating evidence has shown that it is capable of rewiring tumor cells for greater energy flexibility to attain their high energy requirements. This multi-enzyme protein is capable of modulating the function of subcellular organelles for optimal function under different conditions. Apart from lipid metabolism, FASN has functional roles in other cellular processes such as glycolysis and amino acid metabolism. These pivotal roles of FASN in lipid metabolism make it an attractive target in the clinic with several new inhibitors currently being tested in early clinical trials. This article aims to present the current evidence on the emergence of FASN as a target in human malignancies.

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Section: Fasn and Cancermentioning

confidence: 99%

Fatty Acid Synthase: An Emerging Target in Cancer

2020

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“…This pathologically enhanced FA-uptake in OAT in GO, evidenced by limited lipolysis (LIPE) and inducible FA-uptake (LPL), may occur via a depot specific FA transport system, for example, SLC27A6. SLC27A6 belongs to the FAs transporter family to uptake long-chain FAs functioning in heart or non-tumorigenic breast cells and is absent or only expressed at low levels in WAT [27,28].…”

Section: Expression Of a Distinct Fa Transporter In Oatmentioning

confidence: 99%

“…Targeted QPCR analysis of genes highlighted in the whole transcriptome analysis confirmed substantially lower levels of elements of lipid metabolism including lipid uptake (LPL), lipolysis (LIPE) and uFAs conversion (SCD), and substantially up-regulated SLC27A6 (FA transporter) in OAT-H, when compared with WAT ( Figure 5A-D). SLC27A6 has been reported as a transporter for long chain FAs uptake (>14 carbons) [27,28].…”

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confidence: 99%

Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy

Zhang

Evans

Ruhland

et al. 2020

IJMS

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Depot specific expansion of orbital-adipose-tissue (OAT) in Graves’ Orbitopathy (GO) is associated with lipid metabolism signaling defects. We hypothesize that the unique adipocyte biology of OAT facilitates its expansion in GO. A comprehensive comparison of OAT and white-adipose-tissue (WAT) was performed by light/electron-microscopy, lipidomic and transcriptional analysis using ex vivo WAT, healthy OAT (OAT-H) and OAT from GO (OAT-GO). OAT-H/OAT-GO have a single lipid-vacuole and low mitochondrial number. Lower lipolytic activity and smaller adipocytes of OAT-H/OAT-GO, accompanied by similar essential linoleic fatty acid (FA) and (low) FA synthesis to WAT, revealed a hyperplastic OAT expansion through external FA-uptake via abundant SLC27A6 (FA-transporter) expression. Mitochondrial dysfunction of OAT in GO was apparent, as evidenced by the increased mRNA expression of uncoupling protein 1 (UCP1) and mitofusin-2 (MFN2) in OAT-GO compared to OAT-H. Transcriptional profiles of OAT-H revealed high expression of Iroquois homeobox-family (IRX-3&5), and low expression in HOX-family/TBX5 (essential for WAT/BAT (brown-adipose-tissue)/BRITE (BRown-in-whITE) development). We demonstrated unique features of OAT not presented in either WAT or BAT/BRITE. This study reveals that the pathologically enhanced FA-uptake driven hyperplastic expansion of OAT in GO is associated with a depot specific mechanism (the SLC27A6 FA-transporter) and mitochondrial dysfunction. We uncovered that OAT functions as a distinctive fat depot, providing novel insights into adipocyte biology and the pathological development of OAT expansion in GO.

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“…ACADL is involved in catalyzing the final reaction of triglyceride synthesis and its overexpression is frequently observed in patients with obesity and type 2 diabetes [27,28]. Increased abundance of ACSL4, SLC27A6, ELOVL2, and ELOVL4 are involved in anticancer drug resistance, and their aberrant expression leads to metabolism and restoration of lipids and fats, essential for maintenance of cell proliferation [29,30]. High expression of SLC25A17 is involved in sterol synthesis, and its mechanistic regulation has yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Reprogramming and Predominance of Solute Carrier Genes during Acquired Enzalutamide Resistance in Prostate Cancer

Verma

Shankar

Chan

et al. 2020

Cells

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Androgen deprivation therapy (ADT) is standard-of-care for advanced-stage prostate cancer, and enzalutamide (Xtandi®, Astellas, Northbrook, IL, USA), a second generation antiandrogen, is prescribed in this clinical setting. The response to this medication is usually temporary with the rapid emergence of drug resistance. A better understanding of gene expression changes associated with enzalutamide resistance will facilitate circumventing this problem. We compared the transcriptomic profile of paired enzalutamide-sensitive and resistant LNCaP and C4-2B prostate cancer cells for identification of genes involved in drug resistance by performing an unbiased bioinformatics analysis and further validation. Next-Gen sequencing detected 9409 and 7757 genes differentially expressed in LNCaP and C4-2B cells, compared to their parental counterparts. A subset of differentially expressed genes were validated by qRT-PCR. Analysis by the i-pathway revealed membrane transporters including solute carrier proteins, ATP-binding cassette transporters, and drug metabolizing enzymes as the most prominent genes dysregulated in resistant cell lines. RNA-Seq data demonstrated predominance of solute carrier genes SLC12A5, SLC25A17, and SLC27A6 during metabolic reprogramming and development of drug resistance. Upregulation of these genes were associated with higher uptake of lactic/citric acid and lower glucose intake in resistant cells. Our data suggest the predominance of solute carrier genes during metabolic reprogramming of prostate cancer cells in an androgen-deprived environment, thus signifying them as potentially attractive therapeutic targets.

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New Insight on Solute Carrier Family 27 Member 6 (SLC27A6) in Tumoral and Non-Tumoral Breast Cells

Cited by 21 publications

References 38 publications

Fatty Acid Synthase: An Emerging Target in Cancer

Fatty Acid Synthase: An Emerging Target in Cancer

Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy

Metabolic Reprogramming and Predominance of Solute Carrier Genes during Acquired Enzalutamide Resistance in Prostate Cancer

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