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The Role of Hippo Signaling Pathway on Muscle Wasting in ApcMin/+ Mice: A Pilot Study
Author(s) -
Gooden Janesha L,
Lim Benjamin W,
Sato Shuichi
Publication year - 2017
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.31.1_supplement.lb781
Subject(s) - wasting , hippo signaling pathway , cachexia , skeletal muscle , dysferlin , medicine , cancer , endocrinology , signal transduction , denervation , weight loss , biology , microbiology and biotechnology , cancer research , obesity
Cancer cachexia is a wasting syndrome associated with cancer and characterized by progressive weight loss due to excessive loss of skeletal muscle. More than one‐half of all cancer patients is likely to suffer from this syndrome in our country. Despite its high prevalence and importance, cancer cachexia has been overlooked in the clinical settings and the mechanism by which the condition develops needs to be further investigated. The Hippo signaling pathway is found to be involved in determining cell growth and organ size including skeletal muscle in mammals and altered activation of this signaling has been reported in response to external stimuli such as functional overload and denervation. However, to the best of our knowledge, no study has been conducted to examine the role of this signaling during the development of cancer cachexia. The purpose of this study was to determine if Hippo signaling pathway plays a role in cancer cachexia. Age‐matched C57BL6 and ApcMin/+ (Min) mice were used in this study. The body weights of these mice were recorded weekly and muscle weights were determined at the time of sacrifice. The loss of body weight was calculated as a ratio between the peak body weight during the experiment period and the body weight at the time of sacrifice. For western blotting, isolated quadriceps was homogenized by T‐PER tissue protein extraction reagent and protein concentration was determined by Bradford assay. The equal amount of total protein was loaded on 10% acrylamide gel for SDS‐PAGE and transferred to PVDF membrane. Each membrane was blocked with 3% milk in TBST for 45 minutes, followed by primary antibody incubation overnight at 4 °C. After 45 minutes incubation with secondary antibody, the membrane was exposed to ECL for 5 minutes to visualize the bands. The intensity of bands was quantified by Image‐J. The body weights of Min mice began to be lower than control mice at the age of 18 weeks. The average loss of body weight was 13.2 ± 0.7 % in Min mice at the time of sacrifice. Likewise, quadriceps weights were smaller by 39% in cachectic mice compared to healthy control mice. The levels of total MST1 expression in Min mice was elevated compared to that in control mice; however, no difference was observed in the levels of phosphorylated and total YAP protein between two groups. These data indicate not YAP but MST1 may be involved in the progression of muscle wasting due to cancer in mice and inhibition of MST1 may be a potential target to treat cancer cachexia. Support or Funding Information This study was supposed by Summer Research Award at the University of Louisiana at Lafayette (SS).