Metabolism-Related Proteins Are Differentially Expressed according to the Molecular Subtype of Invasive Breast Cancer Defined by Surrogate Immunohistochemistry

Choi, Jong Myung; Jung, Woo Hee; Koo, Ja Seung

doi:10.1159/000339513

Cited by 77 publications

(75 citation statements)

References 109 publications

(64 reference statements)

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“…Various studies have shown that the expression of metabolic enzymes is associated with ER, PR and HER2. Triple-negative breast cancer cells express the highest level of GLUT1 compared to other types of breast cancer cells (12). Immunohistochemistry assay shows that HER2 positive and triple-negative breast cancer cells express relatively high level of glutamate-metabolic enzymes (13).…”

Section: Introductionmentioning

confidence: 95%

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: Introductionmentioning

confidence: 95%

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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“…On the other hand, estrogen-induced HIF-1 accumulation in breast cancer cells stimulates glucose uptake via the PI3K/Akt signaling pathway [19,46] which also leads to increased mTOR phosphorylation [47] . Another clinical study found that HIF-1 had the highest expression in HER-2 positive breast cancer [21] . It indicated that HIF-1 has crosstalk with the ER and HER-2 signal pathways.…”

Section: Targeting Glycolytic Enzymesmentioning

confidence: 98%

“…Different expression patterns of GLUT isoforms in breast cancer may have an association with pathological grade, cancer cell differentiation and prognosis. According to the molecular subtype of invasive breast cancer, HER-2 positive and TNBC mostly exhibit higher levels of glycolysis which need higher levels of expression of GLUT [21] . As the most invasive type in breast cancer, TNBC had the highest expression of GLUT-1 when compared to other types [21] .…”

Section: Metabolic Reprogramming In Breast Cancermentioning

confidence: 99%

“…According to the molecular subtype of invasive breast cancer, HER-2 positive and TNBC mostly exhibit higher levels of glycolysis which need higher levels of expression of GLUT [21] . As the most invasive type in breast cancer, TNBC had the highest expression of GLUT-1 when compared to other types [21] . Increased activity of enzymes involved in glycolysis, like hexokinase (HK) and lactate dehydrogenase-A (LDHA), have also been studied and their expression may affect cancer cell growth [22,23] .…”

Section: Metabolic Reprogramming In Breast Cancermentioning

confidence: 99%

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Targeting metabolism in breast cancer: How far we can go?

Long

Zhang

2016

WJCO

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receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. Core tip: Breast cancer cells display distinct metabolic characteristics according to different molecular phe notypes. There may be crosstalk with the estrogen receptor and human epidermal growth factor receptor2 signal pathways in the metabolic regulation in breast cancer cells that make it more complex to evaluate the efficiency of an antimetabolic drug. On the other hand, the research on target metabolism in breast cancer will also largely help us to understand the complicated mechanism by which an antimetabolic drug impro ves the efficacy of cancer therapy or overcomes drug resistance. AbstractAdjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor MINIREVIEWS 122February 10, 2016|Volume 7|Issue 1|

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“…These molecular differences are associated with histopathological and clinical differences as well as variations in treatment response and prognosis, implicating possible differences in metabolic features. Previous studies indicate elevated expression of the glycolysis-related proteins GLUT-1 and CAIX in basal-like type/TNBC breast cancers [8,9] and elevated expression of the glutaminolysis-related protein in HER-2 type breast cancers [10], supporting a plausible relation between metabolism and molecular subtype. However, the association between breast cancer subtype and sarcosine metabolism-related protein expression has not been examined.…”

Section: Introductionmentioning

confidence: 93%

Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer

2014

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BackgroundThe goal of this study was to investigate the expression of sarcosine metabolism-related proteins, namely glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX), in the different breast cancer subtypes and to assess the implications of differences in expression pattern according to subtype.MethodsWe analyzed the expression of GNMT, SARDH, and PIPOX in a tissue microarray of 721 breast cancer cases using immunohistochemistry (IHC). We classified breast cancer cases into subtype luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) according to the status for the estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67. Sarcosine metabolism phenotype was stratified according to IHC results for GNMT, SARDH, and PIPOX: GNMT(+), SARDH and PIPOX(-) was classified as high sarcosine type; GNMT(-), SARDH or PIPOX(-) as low sarcosine type; GNMT(+), SARDH or PIPOX(+) as intermediate sarcosine type, and GNMT(-), SARDH and PIPOX(-) as null type.ResultsExpression of sarcosine metabolism-related proteins differed significantly according to breast cancer subtype (GNMT, p = 0.005; SARDH, p = 0.012; tumoral PIPOX, p = 0.008; stromal PIPOX, p < 0.001). These proteins were the most frequently expressed in HER-2 type tumors and the least in TNBC. Sarcosine metabolism phenotype also varied according to breast cancer subtype, with high sarcosine type the most common in HER-2, and null type the most common in TNBC (p = 0.003). Univariate analysis revealed that GNMT expression (p = 0.042), tumoral PIPOX negativity (p = 0.039), and high sarcosine type (p = 0.021) were associated with shorter disease-free survival (DFS). Multivariate analysis also revealed GNMT expression was an independent factor for shorter DFS (hazard ratio: 2.408, 95% CI: 1.154-5.024, p = 0.019).ConclusionExpressions of sarcosine metabolism-related proteins varied according to subtype of breast cancer, with HER-2 type tumors showing elevated expression of these proteins, and TNBC subtype showing decreased expression of these proteins. Expression of sarcosine metabolism-related proteins was also associated with breast cancer prognosis.

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Metabolism-Related Proteins Are Differentially Expressed according to the Molecular Subtype of Invasive Breast Cancer Defined by Surrogate Immunohistochemistry

Cited by 77 publications

References 109 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

Targeting metabolism in breast cancer: How far we can go?

Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer

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