Excess TGF-β mediates muscle weakness associated with bone metastases in mice. Nat Med. 2015, 21(11):1262-1271.

報告日期: 2017/04/25
報告時間: 3:10/4:00
報告學生: 陳詠晴
講評老師: 吳佳慶
附件下載: 下載[1629-1487731218-1.pdf] 

Excess TGF-β mediates muscle weakness associated with bone metastases in mice 

David L Waning, et al, Nature Medicine: 1262-71, 2015

Speaker: Yung-Ching Chen                     Date: 2017.04.25 15:10-16:00

Commentator: Chia-Ching Wu, Ph.D.                 Room: 602  

Abstract

Muscle weakness is highly associated with bone metastasis, and there is no available therapy. In this study, the authors used mouse models of human breast or lung cancers which generated osteolytic bone metastases and these tumor-bearing mice developed muscle weakness. The authors also found that transforming growth factor (TGF)-β was released from destructed bone, which increased levels of NADPH oxidase 4 (Nox4) in muscle and resulted in oxidation of muscle protein, including ryanodine receptor and calcium (Ca2+) release channel (RyR1). Oxidized RyR1 contribute to Ca2+ release and impaired muscle contraction. Inhibition of TGF-β signaling, Nox4 activity, or RyR leakage attenuated muscle weakness in cancer metastatic mouse. In conclusion, the authors demonstrate that TGF-β plays a crucial role in cancer-associated muscle weakness, and inhibition of TGF-β/Nox4/RyR1 signaling axis appears to be a promising therapeutic approach to ameliorate muscle weakness in cancer patients with bone metastases. 

Reference

Andersson, D.C. et al. Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging. Cell Metab. 14, 196–207 (2011).