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Proteostasis in the adipose tissue of Cachectic Cancer patients

Grant number: 20/00086-6
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2020
Effective date (End): November 30, 2023
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal researcher:Marilia Cerqueira Leite Seelaender
Grantee:Ana Sayuri Yamagata
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cachexia affects Cancer patients causing involuntary weight loss, which reduces their quality of life and prognosis progressively. The Subcutaneous Adipose Tissue (SAT) is quickly depleted due to high lipolysis and it also participates in the exacerbated inflammatory response, a hallmark of Cancer Cachexia. The SAT produces increased inflammatory cytokines such as Tumor Necrosis Factor alpha (TNF-a) and interleukin 6 (IL-6). Moreover, the activation of the unfolded protein response and the dysfunctional autophagy may be related to the higher production of TNF-a and the activation of the Nuclear Fator kappa B (NFkB) in the SAT as described in animal models of Sepsis and Cachexia. It is also suggested that the activation of Toll-Like Receptors (TLR) and the UPR act synergistically. The activation of TLR4 in the SAT in fundamental for its atrophy and the increase in systemic inflammation in mice with Cancer Cachexia. However, the UPR and the autophagy in the SAT of individuals with Cancer Cachexia have not been studied yet. The evaluation of these pathways can contribute to the understanding of the mechanisms involved in fat loss in Cachexia and indicate therapeutic targets. Therefore, the main objective is to investigate the expression of UPR and autophagy markers in the SAT of gastrointestinal Cancer cachectic patients compared to gastrointestinal Cancer weight stable patients and healthy individuals. (AU)

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Scientific publications
(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)
YAMAGATA, ANA SAYURI; FREIRE, PAULA PACCIELLI. Are cachexia-associated tumors transmitTERS of ER stress?. BIOCHEMICAL SOCIETY TRANSACTIONS, v. 49, n. 4, p. 1841-1853, AUG 2021. Web of Science Citations: 1.

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