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Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1-deficient mouse model of breast cancer metastasis.
Shakri, Ahmad Rushdi; James Zhong, Timothy; Ma, Wanchao; Coker, Courtney; Hegde, Rohaan; Scholze, Hanna; Chin, Vanessa; Szabolcs, Matthias; Hibshoosh, Hanina; Tanji, Kurenai; Baer, Richard; Kumar Biswas, Anup; Acharyya, Swarnali.
Afiliación
  • Shakri AR; Institute for Cancer Genetics, Columbia University, New York, NY, USA.
  • James Zhong T; Institute for Cancer Genetics, Columbia University, New York, NY, USA.
  • Ma W; Graduate School of Arts and Sciences, Department of Pathobiology and Mechanisms of Disease, Columbia University Irving Medical Center, New York, NY, USA.
  • Coker C; Institute for Cancer Genetics, Columbia University, New York, NY, USA.
  • Hegde R; Institute for Cancer Genetics, Columbia University, New York, NY, USA.
  • Scholze H; Department of Biological Sciences, Columbia University, New York, NY, USA.
  • Chin V; Barnard College, Columbia University, New York, NY, USA.
  • Szabolcs M; Weill Cornell Medical College, New York, NY, USA.
  • Hibshoosh H; Barnard College, Columbia University, New York, NY, USA.
  • Tanji K; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
  • Baer R; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
  • Kumar Biswas A; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
  • Acharyya S; Division of Neuropathology, Department of Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
Cancer Med ; 9(18): 6766-6775, 2020 09.
Article en En | MEDLINE | ID: mdl-32730698
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caquexia / Músculo Esquelético / Proteínas de Transporte de Catión / Proteínas Supresoras de Tumor / Ubiquitina-Proteína Ligasas / Neoplasias de la Mama Triple Negativas / Neoplasias Pulmonares Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Cancer Med Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caquexia / Músculo Esquelético / Proteínas de Transporte de Catión / Proteínas Supresoras de Tumor / Ubiquitina-Proteína Ligasas / Neoplasias de la Mama Triple Negativas / Neoplasias Pulmonares Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Cancer Med Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos