Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target
Abnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2023-08-01
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| Series: | Exploration of Medicine |
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| Online Access: | https://www.explorationpub.com/Journals/em/Article/1001160 |
| _version_ | 1797691628193841152 |
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| author | Weimei Xing Xiaowei Li Yuli Zhou Mengsen Li Mingyue Zhu |
| author_facet | Weimei Xing Xiaowei Li Yuli Zhou Mengsen Li Mingyue Zhu |
| author_sort | Weimei Xing |
| collection | DOAJ |
| description | Abnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence of oxygen, a process called aerobic glycolysis, also known as the Warburg effect. Lactate is the end product of the aerobic glycolysis. Lactate dehydrogenase A (LDHA), which is highly expressed in cancer cells, promotes lactate production and transports lactate to the tumor microenvironment and is taken up by surrounding stromal cells under the action of monocarboxylate transporter 1/4 (MCT1/4), which in turn influences the immune response and enhances the invasion and metastasis of cancer cells. Therapeutic strategies targeting lactate metabolism have been intensively investigated, focusing on its metastasis-promoting properties and various target inhibitors; AZD3965, an MCT1 inhibitor, has entered phase I clinical trials, and the LDHA inhibitor N-hydroxyindole (NHI) has shown cancer therapeutic activity in pre-clinical studies. Interventions targeting lactate metabolism are emerging as a promising option for cancer therapy, with chemotherapy or radiotherapy combined with lactate-metabolism-targeted drugs adding to the effectiveness of cancer treatment. Based on current research, this article outlines the role of lactate metabolism in tumor metastasis and the potential value of inhibitors targeting lactate metabolism in cancer therapy. |
| first_indexed | 2024-03-12T02:15:58Z |
| format | Article |
| id | doaj.art-404b70041f43494fbf7aa1979c67c206 |
| institution | Directory Open Access Journal |
| issn | 2692-3106 |
| language | English |
| last_indexed | 2024-03-12T02:15:58Z |
| publishDate | 2023-08-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Medicine |
| spelling | doaj.art-404b70041f43494fbf7aa1979c67c2062023-09-06T08:01:59ZengOpen Exploration Publishing Inc.Exploration of Medicine2692-31062023-08-014454155910.37349/emed.2023.00160Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic targetWeimei Xing0https://orcid.org/0009-0000-3808-4471Xiaowei Li1https://orcid.org/0009-0003-9124-6208Yuli Zhou2https://orcid.org/0009-0007-1815-826XMengsen Li3https://orcid.org/0000-0003-2512-0386Mingyue Zhu4https://orcid.org/0000-0001-5997-4991Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, ChinaHainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, ChinaHainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, ChinaHainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, China; Department of Medical Oncology, Second Affiliated Hospital, Hainan Medical University, Haikou 570311, Hainan, China; Institution of Tumour, First Affiliated Hospital, Hainan Medical University, Haikou 570102, Hainan, ChinaHainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, ChinaAbnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence of oxygen, a process called aerobic glycolysis, also known as the Warburg effect. Lactate is the end product of the aerobic glycolysis. Lactate dehydrogenase A (LDHA), which is highly expressed in cancer cells, promotes lactate production and transports lactate to the tumor microenvironment and is taken up by surrounding stromal cells under the action of monocarboxylate transporter 1/4 (MCT1/4), which in turn influences the immune response and enhances the invasion and metastasis of cancer cells. Therapeutic strategies targeting lactate metabolism have been intensively investigated, focusing on its metastasis-promoting properties and various target inhibitors; AZD3965, an MCT1 inhibitor, has entered phase I clinical trials, and the LDHA inhibitor N-hydroxyindole (NHI) has shown cancer therapeutic activity in pre-clinical studies. Interventions targeting lactate metabolism are emerging as a promising option for cancer therapy, with chemotherapy or radiotherapy combined with lactate-metabolism-targeted drugs adding to the effectiveness of cancer treatment. Based on current research, this article outlines the role of lactate metabolism in tumor metastasis and the potential value of inhibitors targeting lactate metabolism in cancer therapy.https://www.explorationpub.com/Journals/em/Article/1001160lactate metabolismmetastasislactate dehydrogenase amonocarboxylate transporters |
| spellingShingle | Weimei Xing Xiaowei Li Yuli Zhou Mengsen Li Mingyue Zhu Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target Exploration of Medicine lactate metabolism metastasis lactate dehydrogenase a monocarboxylate transporters |
| title | Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target |
| title_full | Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target |
| title_fullStr | Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target |
| title_full_unstemmed | Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target |
| title_short | Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target |
| title_sort | lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target |
| topic | lactate metabolism metastasis lactate dehydrogenase a monocarboxylate transporters |
| url | https://www.explorationpub.com/Journals/em/Article/1001160 |
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