Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism
Efficient catabolic metabolism of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial–mesenchymal transition (EMT) plays an important role in metabolic rewiring...
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doaj-dcfa570883a94936b481bcdad5707d122020-11-25T03:54:06ZengMDPI AGCells2073-44092020-09-0192064206410.3390/cells9092064Breast Cancer Subtypes Underlying EMT-Mediated Catabolic MetabolismEunae Sandra Cho0Nam Hee Kim1Jun Seop Yun2Sue Bean Cho3Hyun Sil Kim4Jong In Yook5Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, KoreaDepartment of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, KoreaDepartment of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, KoreaDepartment of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, KoreaDepartment of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, KoreaDepartment of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, KoreaEfficient catabolic metabolism of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial–mesenchymal transition (EMT) plays an important role in metabolic rewiring of cancer cells as well as in phenotypic conversion and therapeutic resistance. Snail (SNAI1), a well-known inducer of cancer EMT, is critical in providing ATP and NADPH via suppression of several gatekeeper genes involving catabolic metabolism, such as phosphofructokinase 1 (PFK1), fructose-1,6-bisphosphatase 1 (FBP1), and acetyl-CoA carboxylase 2 (ACC2). Paradoxically, FPK1 and FBP1 are counter-opposing and rate-limiting reaction enzymes of glycolysis and gluconeogenesis, respectively. In this study, we report a distinct metabolic circuit of catabolic metabolism in breast cancer subtypes. Interestingly, PFKP and FBP1 are inversely correlated in clinical samples, indicating different metabolic subsets of breast cancer. The luminal types of breast cancer consist of the pentose phosphate pathway (PPP) subset by suppression of PFKP while the basal-like subtype (also known as triple negative breast cancer, TNBC) mainly utilizes glycolysis and mitochondrial fatty acid oxidation (FAO) by loss of FBP1 and ACC2. Notably, PPP remains active via upregulation of TIGAR in the FBP1-loss basal-like subset, indicating the importance of PPP in catabolic cancer metabolism. These results indicate different catabolic metabolic circuits and thus therapeutic strategies in breast cancer subsets.https://www.mdpi.com/2073-4409/9/9/2064SnailEMTcatabolic metabolismbreast cancer subtypes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eunae Sandra Cho Nam Hee Kim Jun Seop Yun Sue Bean Cho Hyun Sil Kim Jong In Yook |
spellingShingle |
Eunae Sandra Cho Nam Hee Kim Jun Seop Yun Sue Bean Cho Hyun Sil Kim Jong In Yook Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism Cells Snail EMT catabolic metabolism breast cancer subtypes |
author_facet |
Eunae Sandra Cho Nam Hee Kim Jun Seop Yun Sue Bean Cho Hyun Sil Kim Jong In Yook |
author_sort |
Eunae Sandra Cho |
title |
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism |
title_short |
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism |
title_full |
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism |
title_fullStr |
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism |
title_full_unstemmed |
Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism |
title_sort |
breast cancer subtypes underlying emt-mediated catabolic metabolism |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-09-01 |
description |
Efficient catabolic metabolism of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) is essentially required for cancer cell survival, especially in metastatic cancer progression. Epithelial–mesenchymal transition (EMT) plays an important role in metabolic rewiring of cancer cells as well as in phenotypic conversion and therapeutic resistance. Snail (SNAI1), a well-known inducer of cancer EMT, is critical in providing ATP and NADPH via suppression of several gatekeeper genes involving catabolic metabolism, such as phosphofructokinase 1 (PFK1), fructose-1,6-bisphosphatase 1 (FBP1), and acetyl-CoA carboxylase 2 (ACC2). Paradoxically, FPK1 and FBP1 are counter-opposing and rate-limiting reaction enzymes of glycolysis and gluconeogenesis, respectively. In this study, we report a distinct metabolic circuit of catabolic metabolism in breast cancer subtypes. Interestingly, PFKP and FBP1 are inversely correlated in clinical samples, indicating different metabolic subsets of breast cancer. The luminal types of breast cancer consist of the pentose phosphate pathway (PPP) subset by suppression of PFKP while the basal-like subtype (also known as triple negative breast cancer, TNBC) mainly utilizes glycolysis and mitochondrial fatty acid oxidation (FAO) by loss of FBP1 and ACC2. Notably, PPP remains active via upregulation of TIGAR in the FBP1-loss basal-like subset, indicating the importance of PPP in catabolic cancer metabolism. These results indicate different catabolic metabolic circuits and thus therapeutic strategies in breast cancer subsets. |
topic |
Snail EMT catabolic metabolism breast cancer subtypes |
url |
https://www.mdpi.com/2073-4409/9/9/2064 |
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