Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer

Chen, Wei Ching; Wang, Chih‐Yang; Hung, Yu Hsuan; Weng, Tzu Yang; Yen, Meng‐Chi; Lai, Ming Derg

doi:10.1371/journal.pone.0155660

Cited by 124 publications

(139 citation statements)

References 85 publications

(91 reference statements)

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“…Recently, a study which use a systematic analysis through public microarray datasets indicated that different types of ACSL isoforms reveal distinct function in different types of cancers, including breast cancer (45). The present study shows that high ACSL1 expression is correlated with poor overall survival rate and high expression levels of ACSL4 and ACSL5 are correlated to good overall survival rate in breast cancer (45).…”

Section: Discussionsupporting

confidence: 55%

“…The present study shows that high ACSL1 expression is correlated with poor overall survival rate and high expression levels of ACSL4 and ACSL5 are correlated to good overall survival rate in breast cancer (45). However, the function of ACSL isoforms were not investigated in different subtypes of breast cancer and the survival analysis was performed in a relatively small cohort.…”

Section: Discussionmentioning

confidence: 80%

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Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

et al. 2017

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Abstract. The lipid metabolic enzymes are considered candidate therapeutic targets for breast cancer. Long-chain acyl-coenzyme A (CoA) synthase (ACSL) is one of lipid metabolic enzymes and converts free-fatty acid to fatty acid-CoA. Five ACSL isoforms including ACSL1, ACSL3, ACSL4, ACSL5 and ACSL6 are identified in human. High ACSL4 expression has been observed in aggressive breast cancer phenotype. However, the role of other isoforms is still little-known. We therefore, analyzed the expression of ACSL isoforms in each subtype of breast cancer within METABRIC dataset and cancer cell line encyclopedia dataset. The expression levels of ACSL1, ACSL4 and ACSL5 in estrogen receptor (ER)-negative group were higher than that in ER-positive group. Similar expression pattern was detected among breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Treatment of ACSL inhibitor triacsin C which inhibited enzyme activity of ACSL 1, 3, 4 and 5 suppressed cell growth of MCF-7 and MDA-MB-231. Our results further showed that high ACSL5 expression was associated with good prognosis in patients with both ER-positive and ER-negative breast cancer through KM plotter analysis. These results suggest that ACSL1, ACSL4 and ACSL5 expression is regulated by ER signaling pathways and ACSL5 is a potential novel biomarker for predicting prognosis of breast cancer patients.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 80%

Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

et al. 2017

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“…Its role is to activate long chain fatty acids during synthesis of acyl-CoA and is the first committed step in fatty acid metabolism. Upregulation of both ACSL1 and LPL expression has been demonstrated in BrCa and correlate negatively with overall survival [28][29][30]. In addition to meeting the cell's energy demands, lipid metabolism also provides substrates for membrane lipid generation.…”

Section: Discussionmentioning

confidence: 99%

Perturbation of the gut microbiota by antibiotics results in accelerated breast tumour growth and metabolic dysregulation

Kirkup

McKee

Makin

et al. 2019

Preprint

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Background: Breast cancer is the second most prevalent cancer worldwide with around 1.7 million new cases diagnosed every year. Whilst prognosis is generally favourable in early stages, this worsens significantly in advanced disease. Therefore, it is pertinent to focus on mitigating factors that may slow growth or progression. Recently, the gut microbiome has been implicated in a wide-range of roles in tumour biology. Through modulation of immunity, the gut microbiota can improve the efficacy of several immunotherapies. However, despite the prevalence of breast cancer, there is still a lack of microbiota studies in this field, including exploring the influence of external microbiome-modulating factors such as antibiotics. We describe herein how disruption of the gut microbiota via antibiotics may be detrimental to patient outcomes through acceleration of tumour growth. Results:Supplementing animals with a cocktail of antibiotics leads to gut microbiota alterations and is accompanied by significant acceleration of tumour growth. Surprisingly, and distinct from previous microbiome-tumour studies, the mechanism driving these effects do not appear to be due to gross immunological changes. Analysis of intratumoural immune cell populations and cytokine production are not affected by antibiotic administration. Through global tumour transcriptomics, we have uncovered dysregulated gene expression networks relating to protein and lipid metabolism that are correlated with accelerated tumour growth.Fecal metabolomics revealed a reduction of the microbial-derived short-chain fatty acid butyrate that may contribute to accelerated tumour growth. Finally, through use of a routinely administered antibiotic in breast cancer patients, Cephalexin, we have shown that tumour growth is also significantly affected. Metataxanomic sequencing and analysis highlighted significant antibiotic-associated reductions in the butyrate producing genera Odoribacter and Anaeotruncus, and increased abundance of Bacteroides. Conclusions:Our data indicate that perturbation of the microbiota by antibiotics may have negative impacts on breast cancer patient outcomes. This is of importance as antibiotics are regularly prescribed to breast cancer patients undergoing mastectomy or breast reconstruction. We have also shown that the metabolic impact of disruption to the microbiome should be considered alongside the potent immunological effects. We believe our work lays the foundation for improving the use of antibiotics in patients, and with further investigation could potentially inform clinical practice.

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“…Highly proliferative cells require large amounts of fatty acid building blocks from exogenous sources and/or de novo synthesis to sustain the building of cell membranes and organelles. For example, previous reports suggest that the upregulation of acyl-CoA synthetase ACSL4 promotes tumor cell survival in human colon adenocarcinomas [62], and that fatty acid-binding proteins can channel lipids from surrounding tissues to fuel further tumor growth [63]. Future metabolomic studies will be needed to further elucidate the DDX5-FABP1 dependent lipidome in the small intestine IECs.…”

Section: Discussionmentioning

confidence: 99%

DDX5 targets tissue-specific RNAs to promote intestine tumorigenesis

Abbasi

Long

et al. 2020

Preprint

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Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that an RNA binding protein DDX5 augments C3 and FABP1 expressions post-transcriptionally to promote tumorigenesis in the colon and small intestine, respectively. Mice with epithelial-specific knockout of DDX5 are protected from intestine tumorigenesis. The identification of DDX5 as the common upstream regulator of tissue-specific oncogenic molecules provides a new therapeutic target for intestine cancers.

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Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer

Cited by 124 publications

References 85 publications

Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

Perturbation of the gut microbiota by antibiotics results in accelerated breast tumour growth and metabolic dysregulation

DDX5 targets tissue-specific RNAs to promote intestine tumorigenesis

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