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Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia
Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug re...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645730/ https://www.ncbi.nlm.nih.gov/pubmed/34533861 http://dx.doi.org/10.1111/cas.15138 |
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author | Saito, Yusuke Kinoshita, Mariko Yamada, Ai Kawano, Sayaka Liu, Hong‐Shan Kamimura, Sachiyo Nakagawa, Midori Nagasawa, Syun Taguchi, Tadao Yamada, Shuhei Moritake, Hiroshi |
author_facet | Saito, Yusuke Kinoshita, Mariko Yamada, Ai Kawano, Sayaka Liu, Hong‐Shan Kamimura, Sachiyo Nakagawa, Midori Nagasawa, Syun Taguchi, Tadao Yamada, Shuhei Moritake, Hiroshi |
author_sort | Saito, Yusuke |
collection | PubMed |
description | Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene‐independent leukemia. |
format | Online Article Text |
id | pubmed-8645730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86457302021-12-17 Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia Saito, Yusuke Kinoshita, Mariko Yamada, Ai Kawano, Sayaka Liu, Hong‐Shan Kamimura, Sachiyo Nakagawa, Midori Nagasawa, Syun Taguchi, Tadao Yamada, Shuhei Moritake, Hiroshi Cancer Sci Original Articles Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene‐independent leukemia. John Wiley and Sons Inc. 2021-10-12 2021-12 /pmc/articles/PMC8645730/ /pubmed/34533861 http://dx.doi.org/10.1111/cas.15138 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Saito, Yusuke Kinoshita, Mariko Yamada, Ai Kawano, Sayaka Liu, Hong‐Shan Kamimura, Sachiyo Nakagawa, Midori Nagasawa, Syun Taguchi, Tadao Yamada, Shuhei Moritake, Hiroshi Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
title | Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
title_full | Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
title_fullStr | Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
title_full_unstemmed | Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
title_short | Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
title_sort | mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645730/ https://www.ncbi.nlm.nih.gov/pubmed/34533861 http://dx.doi.org/10.1111/cas.15138 |
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