Molecular mechanisms underlying cancer cachexia: exploring the role of COPS2

• Grant number: 16/01478-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: April 30, 2016
• End date: October 29, 2016
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Patricia Chakur Brum
• Grantee: Christiano Robles Rodrigues Alves
• Supervisor: Laurie Goodyear
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 14/03016-8 - Cancer cachexia: effects of aerobic physical training on skeletal muscle in animal model, BP.DD

Abstract

Cachexia syndrome remains as a key problem for cancer patients. Importantly, the molecular basis of cancer cachexia is complex and still poorly understood. Recently, we found that high-intensity interval training (HIIT) improves exercise capacity and increases survival in a severe cancer cachexia rat model. Importantly, HIIT fully restored skeletal muscle function and redox balance to the control levels. Using proteomics screening we identified the protein COPS2 extremely reduced in skeletal muscle of cancer cachexia models and fully restored by HIIT. Therefore, the aim of this study is to explore the putative role of COPS2 for skeletal muscle metabolic homeostasis through COPS2 gene overexpression and ablation in vitro and in vivo. Additionally, we aim to test whether COPS2 mRNA levels will be altered in other models of metabolic impairment. In order to perform these experiments, we propose an internship at Joslin Diabetes Center, Harvard Medical School (Boston, US) under Dr. Laurie Goodyear supervision. This collaboration fits perfect in order to achieve our goals since Dr. Goodyear´s group has expertise in molecular and physiological approaches in rodent skeletal muscles in vitro and in vivo, including experiments overexpressing proteins into adult rodent skeletal muscle by electroporation. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALVES, CHRISTIANO R. R.; NEVES, WILLIAN DAS; ALMEIDA, NEY R. DE; EICHELBERGER, ERIC J.; JANNIG, PAULO R.; VOLTARELLI, VANESSA A.; TOBIAS, GABRIEL C.; BECHARA, LUIZ R. G.; FARIA, DANIELE DE PAULA; ALVES, MARIA J. N.; et al. Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/ TRIP15/ALIEN. MOLECULAR METABOLISM, v. 39, SEP 2020. (16/50336-3, 12/02528-0, 14/03016-8, 12/25240-1, 15/22814-5, 16/01478-0, 16/20187-6)

ALVES, CHRISTIANO R. R.; EICHELBERGER, ERIC J.; DAS NEVES, WILLIAN; RIBEIRO, MARCIO A. C.; BECHARA, LUIZ R. G.; VOLTARELLI, VANESSA A.; DE ALMEIDA, NEY R.; HAGEN, LARS; SHARMA, ANIMESH; FERREIRA, JULIO C. B.; et al. Cancer-induced muscle atrophy is determined by intrinsic muscle oxidative capacity. FASEB JOURNAL, v. 35, n. 7, JUL 2021. (16/50336-3, 16/01478-0, 12/25240-1, 16/20187-6, 15/22814-5, 14/03016-8, 12/02528-0)

ALVES, CHRISTIANO; GOODYEAR, LAURIE; BRUM, PATRICIA. Muscle metabolic stress determines cancer cachexia severity in mice. FRONTIERS IN PHYSIOLOGY, v. 13, p. 7-pg., 2022-11-28. (14/03016-8, 12/25240-1, 12/02528-0, 15/22814-5, 16/01478-0)

ALVES, CHRISTIANO R. R.; FARIA, DANIELE DE P.; CARNEIRO, CAMILA DE G.; GARCEZ, ALEXANDRE T.; GUTIERREZ, VANESSA P.; DAS NEVES, WILLIAN; DE ALMEIDA, NEY R.; CURY, YARA; CHAMMAS, ROGER; BRUM, PATRICIA C.. F-18-Fluoride PET/CT and Tc-99m-MDP SPECT/CT can detect bone cancer at early stage in rodents. Life Sciences, v. 206, p. 29-34, AUG 1 2018. (15/22814-5, 14/03016-8, 16/01478-0, 12/02528-0, 12/25240-1)

DAS NEVES, WILLIAN; ALVES, CHRISTIANO R. R.; DE SOUZA BORGES, ANA PAULA; DE CASTRO JR, GILBERTO. Serum Creatinine as a Potential Biomarker of Skeletal Muscle Atrophy in Non-small Cell Lung Cancer Patients. FRONTIERS IN PHYSIOLOGY, v. 12, APR 12 2021. (15/22814-5, 14/03016-8, 12/25240-1, 12/02528-0, 16/01478-0)

ALVES, CHRISTIANO R. R.; DAS NEVES, WILLIAN; DE ALMEIDA, NEY R.; EICHELBERGER, ERIC J.; JANNIG, PAULO R.; VOLTARELLI, VANESSA A.; TOBIAS, GABRIEL C.; BECHARA, LUIZ R. G.; FARIA, DANIELE DE PAULA; ALVES, MARIA J. N.; et al. Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/TRIP15/ALIEN. MOLECULAR METABOLISM, v. 39, p. 17-pg., 2020-09-01. (16/50336-3, 14/03016-8, 16/20187-6, 12/25240-1, 16/01478-0, 15/22814-5, 12/02528-0)