The role of lactylation in tumor growth and cancer progression
BackgroundLactate’s perception of lactate has changed over the last 30 years from a straightforward metabolic byproduct to a complex chemical with important biological activities, such as signal transduction, gluconeogenesis, and mitochondrial respiration. In addition to its metabolic contributions,...
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| Format: | Article |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1516785/full |
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| author | Khulood Al-Malsi Khulood Al-Malsi Khulood Al-Malsi Sinan Xie Sinan Xie Sinan Xie Yunshi Cai Yunshi Cai Yunshi Cai Nader Mohammed Kunlin Xie Kunlin Xie Kunlin Xie Tian Lan Tian Lan Tian Lan Hong Wu Hong Wu Hong Wu |
| author_facet | Khulood Al-Malsi Khulood Al-Malsi Khulood Al-Malsi Sinan Xie Sinan Xie Sinan Xie Yunshi Cai Yunshi Cai Yunshi Cai Nader Mohammed Kunlin Xie Kunlin Xie Kunlin Xie Tian Lan Tian Lan Tian Lan Hong Wu Hong Wu Hong Wu |
| author_sort | Khulood Al-Malsi |
| collection | DOAJ |
| description | BackgroundLactate’s perception of lactate has changed over the last 30 years from a straightforward metabolic byproduct to a complex chemical with important biological activities, such as signal transduction, gluconeogenesis, and mitochondrial respiration. In addition to its metabolic contributions, lactate has far-reaching repercussions. This review highlights the role of lactate in the course of cancer by highlighting lactylation as a unique epigenetic alteration. The purpose of this review is to clarify the functions of lactate in the biology of tumors, with a particular focus on the translational potential of lactylation pathways in cancer diagnosis and treatment approaches.MethodsThis review summarizes research on the relationship between lactate and cancer, with an emphasis on histone lactylation, its effect on gene expression, and its influence on the tumor microenvironment. By establishing a connection between metabolic byproducts and epigenetic gene regulation, we investigated how lactylation affects immune regulation, inflammation, and cellular repair.FindingsHistone lactylation, or the addition of lactate to lysine residues on histone proteins, increases transcriptional activity and facilitates the expression of genes involved in homeostasis and repair. These findings have important implications for cancer treatment. Lactylation, for example, activates genes such as Arg1, which is a hallmark of the M2 macrophage phenotype implicated in immunosuppression and tumor growth. The ability of lactate to dynamically alter gene expression is further supported by its function as a histone deacetylase(HDAC)inhibitor and its impact on histone acetylation. Its wide-ranging involvement in cellular metabolism and epigenetic control has been demonstrated by the discovery of particular lactylation sites on histones in various cell types, including cancer cells. |
| format | Article |
| id | doaj-art-2aa974eef5044138acb0f1595abb2b67 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-2aa974eef5044138acb0f1595abb2b672025-02-04T05:28:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-02-011510.3389/fonc.2025.15167851516785The role of lactylation in tumor growth and cancer progressionKhulood Al-Malsi0Khulood Al-Malsi1Khulood Al-Malsi2Sinan Xie3Sinan Xie4Sinan Xie5Yunshi Cai6Yunshi Cai7Yunshi Cai8Nader Mohammed9Kunlin Xie10Kunlin Xie11Kunlin Xie12Tian Lan13Tian Lan14Tian Lan15Hong Wu16Hong Wu17Hong Wu18Department of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLiver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLiver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLiver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaEmergency Department Research, Hamad Medical Corporation, Doha, QatarDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLiver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLiver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLiver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundLactate’s perception of lactate has changed over the last 30 years from a straightforward metabolic byproduct to a complex chemical with important biological activities, such as signal transduction, gluconeogenesis, and mitochondrial respiration. In addition to its metabolic contributions, lactate has far-reaching repercussions. This review highlights the role of lactate in the course of cancer by highlighting lactylation as a unique epigenetic alteration. The purpose of this review is to clarify the functions of lactate in the biology of tumors, with a particular focus on the translational potential of lactylation pathways in cancer diagnosis and treatment approaches.MethodsThis review summarizes research on the relationship between lactate and cancer, with an emphasis on histone lactylation, its effect on gene expression, and its influence on the tumor microenvironment. By establishing a connection between metabolic byproducts and epigenetic gene regulation, we investigated how lactylation affects immune regulation, inflammation, and cellular repair.FindingsHistone lactylation, or the addition of lactate to lysine residues on histone proteins, increases transcriptional activity and facilitates the expression of genes involved in homeostasis and repair. These findings have important implications for cancer treatment. Lactylation, for example, activates genes such as Arg1, which is a hallmark of the M2 macrophage phenotype implicated in immunosuppression and tumor growth. The ability of lactate to dynamically alter gene expression is further supported by its function as a histone deacetylase(HDAC)inhibitor and its impact on histone acetylation. Its wide-ranging involvement in cellular metabolism and epigenetic control has been demonstrated by the discovery of particular lactylation sites on histones in various cell types, including cancer cells.https://www.frontiersin.org/articles/10.3389/fonc.2025.1516785/fulllactylationtumor microenvironmentcancer metabolismepigenetic regulationhistoneepigenetic modification |
| spellingShingle | Khulood Al-Malsi Khulood Al-Malsi Khulood Al-Malsi Sinan Xie Sinan Xie Sinan Xie Yunshi Cai Yunshi Cai Yunshi Cai Nader Mohammed Kunlin Xie Kunlin Xie Kunlin Xie Tian Lan Tian Lan Tian Lan Hong Wu Hong Wu Hong Wu The role of lactylation in tumor growth and cancer progression Frontiers in Oncology lactylation tumor microenvironment cancer metabolism epigenetic regulation histone epigenetic modification |
| title | The role of lactylation in tumor growth and cancer progression |
| title_full | The role of lactylation in tumor growth and cancer progression |
| title_fullStr | The role of lactylation in tumor growth and cancer progression |
| title_full_unstemmed | The role of lactylation in tumor growth and cancer progression |
| title_short | The role of lactylation in tumor growth and cancer progression |
| title_sort | role of lactylation in tumor growth and cancer progression |
| topic | lactylation tumor microenvironment cancer metabolism epigenetic regulation histone epigenetic modification |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1516785/full |
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