Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer
Branched-chain amino acids (BCAAs) are the three essential amino acids including leucine, isoleucine, and valine. BCAA metabolism has been linked with the development of a variety of tumors. However, the impact of dietary BCAA intake on breast tumor progression and metastasis remains to be fully exp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.887257/full |
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| author | Rui Chi Chengcheng Yao Si Chen Yunxia Liu Yanqi He Jin Zhang Lesley G. Ellies Xuefeng Wu Qian Zhao Cixiang Zhou Ying Wang Haipeng Sun Haipeng Sun |
| author_facet | Rui Chi Chengcheng Yao Si Chen Yunxia Liu Yanqi He Jin Zhang Lesley G. Ellies Xuefeng Wu Qian Zhao Cixiang Zhou Ying Wang Haipeng Sun Haipeng Sun |
| author_sort | Rui Chi |
| collection | DOAJ |
| description | Branched-chain amino acids (BCAAs) are the three essential amino acids including leucine, isoleucine, and valine. BCAA metabolism has been linked with the development of a variety of tumors. However, the impact of dietary BCAA intake on breast tumor progression and metastasis remains to be fully explored. Here, we unexpectedly find that the elevated BCAA, either in the genetic model or via increasing dietary intake in mice, suppresses the tumor growth and lung metastasis of breast cancer. The survival analysis shows that BCAA catabolic gene expression is strongly associated with long-term oncological outcomes in patients with breast cancer. In Pp2cm knockout mice in which BCAAs accumulate due to the genetic defect of BCAA catabolism, the breast tumor growth is suppressed. Interestingly, while the cell proliferation and tumor vasculature remain unaffected, more cell death occurs in the tumor in Pp2cm knockout mice, accompanied with increased natural killer (NK) cells. Importantly, increasing BCAA dietary intake suppresses breast tumor growth in mice. On the other hand, there are fewer lung metastases from primary breast tumor in Pp2cm knockout mice and the high BCAA diet-fed mice, suggesting high BCAA also suppresses the lung metastasis of breast cancer. Furthermore, low BCAA diet promotes lung colonization of breast cancer cells in tail vein model. The migration and invasion abilities of breast cancer cells are impaired by high concentration of BCAA in culture medium. The suppressed tumor metastasis and cell migration/invasion abilities by elevated BCAA are accompanied with reduced N-cadherin expression. Together, these data show high BCAA suppresses both tumor growth and metastasis of breast cancer, demonstrating the potential benefits of increasing BCAA dietary intake in the treatment of breast cancer. |
| first_indexed | 2024-04-12T14:50:03Z |
| format | Article |
| id | doaj.art-c14c21b93877442ca7dcda6299be708a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T14:50:03Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c14c21b93877442ca7dcda6299be708a2022-12-22T03:28:30ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.887257887257Elevated BCAA Suppresses the Development and Metastasis of Breast CancerRui Chi0Chengcheng Yao1Si Chen2Yunxia Liu3Yanqi He4Jin Zhang5Lesley G. Ellies6Xuefeng Wu7Qian Zhao8Cixiang Zhou9Ying Wang10Haipeng Sun11Haipeng Sun12Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaHongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, United StatesShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaNHC Key Laboratory of Hormones and Development, Center for Cardiovascular Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaBranched-chain amino acids (BCAAs) are the three essential amino acids including leucine, isoleucine, and valine. BCAA metabolism has been linked with the development of a variety of tumors. However, the impact of dietary BCAA intake on breast tumor progression and metastasis remains to be fully explored. Here, we unexpectedly find that the elevated BCAA, either in the genetic model or via increasing dietary intake in mice, suppresses the tumor growth and lung metastasis of breast cancer. The survival analysis shows that BCAA catabolic gene expression is strongly associated with long-term oncological outcomes in patients with breast cancer. In Pp2cm knockout mice in which BCAAs accumulate due to the genetic defect of BCAA catabolism, the breast tumor growth is suppressed. Interestingly, while the cell proliferation and tumor vasculature remain unaffected, more cell death occurs in the tumor in Pp2cm knockout mice, accompanied with increased natural killer (NK) cells. Importantly, increasing BCAA dietary intake suppresses breast tumor growth in mice. On the other hand, there are fewer lung metastases from primary breast tumor in Pp2cm knockout mice and the high BCAA diet-fed mice, suggesting high BCAA also suppresses the lung metastasis of breast cancer. Furthermore, low BCAA diet promotes lung colonization of breast cancer cells in tail vein model. The migration and invasion abilities of breast cancer cells are impaired by high concentration of BCAA in culture medium. The suppressed tumor metastasis and cell migration/invasion abilities by elevated BCAA are accompanied with reduced N-cadherin expression. Together, these data show high BCAA suppresses both tumor growth and metastasis of breast cancer, demonstrating the potential benefits of increasing BCAA dietary intake in the treatment of breast cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.887257/fullbranched-chain amino acidbreast cancerNK cellmetastasisN-Cadherin |
| spellingShingle | Rui Chi Chengcheng Yao Si Chen Yunxia Liu Yanqi He Jin Zhang Lesley G. Ellies Xuefeng Wu Qian Zhao Cixiang Zhou Ying Wang Haipeng Sun Haipeng Sun Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer Frontiers in Oncology branched-chain amino acid breast cancer NK cell metastasis N-Cadherin |
| title | Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer |
| title_full | Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer |
| title_fullStr | Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer |
| title_full_unstemmed | Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer |
| title_short | Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer |
| title_sort | elevated bcaa suppresses the development and metastasis of breast cancer |
| topic | branched-chain amino acid breast cancer NK cell metastasis N-Cadherin |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.887257/full |
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