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Skeletal muscle PI3K/Akt signaling and ubiquitin‐related enzyme mRNA expression in lung cancer cachexia
Author(s) -
Chevalier Stephanie,
Burgos Sergio,
Mehrfar Parisa,
Bédard Nathalie,
Altit Gabriel,
Marliss Errol B.,
Wing Simon S.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1059.21
Subject(s) - protein kinase b , cachexia , pi3k/akt/mtor pathway , lung cancer , skeletal muscle , endocrinology , medicine , cancer research , signal transduction , biology , cancer , microbiology and biotechnology
The progressive loss of muscle mass is common in lung cancer. Objective to assess possible changes in signal transduction events that regulate protein synthesis and degradation in skeletal muscle of patients with early lung cancer. Muscle biopsies and blood samples were collected from non‐small cell lung cancer (NSCLC) subjects, 8 with and 8 without cachexia, and 8 non‐cancer controls undergoing thoracic surgery. The abundance and phosphorylation of proteins of the PI3K/Akt signaling pathway were measured by immunoblotting and expression of ubiquitin ligases and deubiquitinating enzyme USP19 mRNA, by RT‐qPCR. Cachectic patients had lost 11.5 ± 1.9% body weight, had lower lean and fat mass and higher serum C‐reactive protein, IL‐6 and IL‐8. Phospho‐PRAS40 Thr246 and p‐FoxO1/3a Thr24/32 were higher in cachectic than in other groups, despite similar p‐Akt Ser473 , but Akt, PRAS40 and FoxO3a abundance was lower. The abundance of the translational inhibitor eukaryotic initiation factor (eIF) 4E binding protein (4E‐BP1) was 65% higher than in controls ( P =0.009); eIF4E abundance did not differ. MuRF‐1, MAFbx and USP19 mRNA expression was not different among groups. Data show lower expression of components of the PI3K/Akt signaling pathway and greater abundance of 4E‐BP1 in early NSCLC cachexia that may indicate decreased mRNA translation in skeletal muscle, which in turn, could lead to muscle loss. (Funded by CIHR)