Abstract
Fatty acid metabolism is important in the regulation of breast cancer progression. Some of the proteins involved in fatty acid transport have been demonstrated to promote the proliferation, migration, and invasion in breast cancer cells. Solute carrier family 27 member 4 (SLC27A4) is a fatty acid transporter protein and is related to very long chain acyl-CoA synthetase activity. In the present study, bioinformatic analysis revealed that relatively high SLC27A4 expression was observed in all subtypes of breast tumor tissues when compared to normal breast tissues. Silencing SLC27A4 expression significantly reduced uptake of free fatty acids in two breast cancer cell lines, Hs578T and MDA-MB-231. Cell growth inhibition was observed in SLC27A4-silenced Hs578T and cell cycle was arrested at G2/M. In addition, the capacity of migration and invasion decreased in both cell lines after knockdown of SLC27A4. The epithelial–mesenchymal transition signaling pathway was inhibited because protein expression of Slug, vimentin, α-smooth muscle actin, and other regulators was lower than that in control cells. Taken together, our results confirm that high SLC27A4 is associated with tumor progression in breast cancer cells. It is worth investigating whether SLC27A4 serves a diagnostic marker and therapeutic target in further studies.
Highlights
Among all types of women’s cancers, breast cancer has the most new cases of diagnosed cancer type and is the second cause of cancer-related mortality worldwide [1]
The aim of this study is to investigate whether solute carrier family 27 (SLC27) family proteins are associated with progression of breast cancer, including cell growth, migration, invasion, and potential regulatory mechanism in breast cancer cells
There is a trend toward shorter overall survival and distant metastasis-free survival in breast cancer patients with higher SLC27A4 expression (Figure 1c,d, p = 0.0725 and 0.033 respectively)
Summary
Among all types of women’s cancers, breast cancer has the most new cases of diagnosed cancer type and is the second cause of cancer-related mortality worldwide [1]. Fatty acid metabolism comprises multiple pathways including fatty acid transport, de novo synthesis, fatty acid oxidation, etc., and emerging evidence has indicated that some of the fatty acid metabolic enzymes are related to different subtypes of breast cancer [3]. High ACSL4 expression is inversely associated with estrogen receptor expression and high ACSL4 expression is a biomarker for an aggressive breast cancer phenotype [7,8,9]. These enzymes might serve as therapeutic targets and diagnostic markers in different subtypes of breast cancer
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