Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis
Abstract Nearly 80% of advanced cancer patients are afflicted with cachexia, a debilitating syndrome characterized by extensive loss of muscle mass and function. Cachectic cancer patients have a reduced tolerance to antineoplastic therapies and often succumb to premature death from the wasting of re...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3242 |
| _version_ | 1828832354909552640 |
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| author | Ahmad Rushdi Shakri Timothy James Zhong Wanchao Ma Courtney Coker Rohaan Hegde Hanna Scholze Vanessa Chin Matthias Szabolcs Hanina Hibshoosh Kurenai Tanji Richard Baer Anup Kumar Biswas Swarnali Acharyya |
| author_facet | Ahmad Rushdi Shakri Timothy James Zhong Wanchao Ma Courtney Coker Rohaan Hegde Hanna Scholze Vanessa Chin Matthias Szabolcs Hanina Hibshoosh Kurenai Tanji Richard Baer Anup Kumar Biswas Swarnali Acharyya |
| author_sort | Ahmad Rushdi Shakri |
| collection | DOAJ |
| description | Abstract Nearly 80% of advanced cancer patients are afflicted with cachexia, a debilitating syndrome characterized by extensive loss of muscle mass and function. Cachectic cancer patients have a reduced tolerance to antineoplastic therapies and often succumb to premature death from the wasting of respiratory and cardiac muscles. Since there are no available treatments for cachexia, it is imperative to understand the mechanisms that drive cachexia in order to devise effective strategies to treat it. Although 25% of metastatic breast cancer patients develop symptoms of muscle wasting, mechanistic studies of breast cancer cachexia have been hampered by a lack of experimental models. Using tumor cells deficient for BARD1, a subunit of the BRCA1/BARD1 tumor suppressor complex, we have developed a new orthotopic model of triple‐negative breast cancer that spontaneously metastasizes to the lung and leads to systemic muscle deterioration. We show that expression of the metal‐ion transporter, Zip14, is markedly upregulated in cachectic muscles from these mice and is associated with elevated intramuscular zinc and iron levels. Aberrant Zip14 expression and altered metal‐ion homeostasis could therefore represent an underlying mechanism of cachexia development in human patients with triple‐negative breast cancer. Our study provides a unique model for studying breast cancer cachexia and identifies a potential therapeutic target for its treatment. |
| first_indexed | 2024-12-12T16:52:32Z |
| format | Article |
| id | doaj.art-21f364a05f8948c6935977c5eace599f |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-12T16:52:32Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-21f364a05f8948c6935977c5eace599f2022-12-22T00:18:20ZengWileyCancer Medicine2045-76342020-09-019186766677510.1002/cam4.3242Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasisAhmad Rushdi Shakri0Timothy James Zhong1Wanchao Ma2Courtney Coker3Rohaan Hegde4Hanna Scholze5Vanessa Chin6Matthias Szabolcs7Hanina Hibshoosh8Kurenai Tanji9Richard Baer10Anup Kumar Biswas11Swarnali Acharyya12Institute for Cancer Genetics Columbia University New York NY USAInstitute for Cancer Genetics Columbia University New York NY USAInstitute for Cancer Genetics Columbia University New York NY USAInstitute for Cancer Genetics Columbia University New York NY USADepartment of Biological Sciences Columbia University New York NY USABarnard CollegeColumbia University New York NY USABarnard CollegeColumbia University New York NY USADepartment of Pathology and Cell Biology Columbia University New York NY USADepartment of Pathology and Cell Biology Columbia University New York NY USADivision of Neuropathology Department of Pathology and Cell Biology Columbia University Medical Center and New York Presbyterian Hospital New York NY USAInstitute for Cancer Genetics Columbia University New York NY USAInstitute for Cancer Genetics Columbia University New York NY USAInstitute for Cancer Genetics Columbia University New York NY USAAbstract Nearly 80% of advanced cancer patients are afflicted with cachexia, a debilitating syndrome characterized by extensive loss of muscle mass and function. Cachectic cancer patients have a reduced tolerance to antineoplastic therapies and often succumb to premature death from the wasting of respiratory and cardiac muscles. Since there are no available treatments for cachexia, it is imperative to understand the mechanisms that drive cachexia in order to devise effective strategies to treat it. Although 25% of metastatic breast cancer patients develop symptoms of muscle wasting, mechanistic studies of breast cancer cachexia have been hampered by a lack of experimental models. Using tumor cells deficient for BARD1, a subunit of the BRCA1/BARD1 tumor suppressor complex, we have developed a new orthotopic model of triple‐negative breast cancer that spontaneously metastasizes to the lung and leads to systemic muscle deterioration. We show that expression of the metal‐ion transporter, Zip14, is markedly upregulated in cachectic muscles from these mice and is associated with elevated intramuscular zinc and iron levels. Aberrant Zip14 expression and altered metal‐ion homeostasis could therefore represent an underlying mechanism of cachexia development in human patients with triple‐negative breast cancer. Our study provides a unique model for studying breast cancer cachexia and identifies a potential therapeutic target for its treatment.https://doi.org/10.1002/cam4.3242BRCA mutationsbreast cancercachexiametastasismouse models |
| spellingShingle | Ahmad Rushdi Shakri Timothy James Zhong Wanchao Ma Courtney Coker Rohaan Hegde Hanna Scholze Vanessa Chin Matthias Szabolcs Hanina Hibshoosh Kurenai Tanji Richard Baer Anup Kumar Biswas Swarnali Acharyya Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis Cancer Medicine BRCA mutations breast cancer cachexia metastasis mouse models |
| title | Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis |
| title_full | Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis |
| title_fullStr | Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis |
| title_full_unstemmed | Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis |
| title_short | Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1‐deficient mouse model of breast cancer metastasis |
| title_sort | aberrant zip14 expression in muscle is associated with cachexia in a bard1 deficient mouse model of breast cancer metastasis |
| topic | BRCA mutations breast cancer cachexia metastasis mouse models |
| url | https://doi.org/10.1002/cam4.3242 |
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