Group I Paks support muscle regeneration and counteract cancer-associated muscle atrophy

Journal of Cachexia, Sarcopenia and Muscle
Andrea Cerquone PerpetuiniGianni Cesareni

Abstract

Skeletal muscle is characterized by an efficient regeneration potential that is often impaired during myopathies. Understanding the molecular players involved in muscle homeostasis and regeneration could help to find new therapies against muscle degenerative disorders. Previous studies revealed that the Ser/Thr kinase p21 protein-activated kinase 1 (Pak1) was specifically down-regulated in the atrophying gastrocnemius of Yoshida hepatoma-bearing rats. In this study, we evaluated the role of group I Paks during cancer-related atrophy and muscle regeneration. We examined Pak1 expression levels in the mouse Tibialis Anterior muscles during cancer cachexia induced by grafting colon adenocarcinoma C26 cells and in vitro by dexamethasone treatment. We investigated whether the overexpression of Pak1 counteracts muscle wasting in C26-bearing mice and in vitro also during interleukin-6 (IL6)-induced or dexamethasone-induced C2C12 atrophy. Moreover, we analysed the involvement of group I Paks on myogenic differentiation in vivo and in vitro using the group I chemical inhibitor IPA-3. We found that Pak1 expression levels are reduced during cancer-induced cachexia in the Tibialis Anterior muscles of colon adenocarcinoma C26-bearing mice an...Continue Reading

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Citations

May 12, 2019·Cells·Lisbeth Liliendal Valbjørn MøllerLykke Sylow
Feb 14, 2020·Expert Opinion on Drug Discovery·Tsuyoshi SuzukiJochen Springer
Mar 21, 2019·Current Opinion in Oncology·Josep M ArgilésFrancisco Javier López-Soriano
Oct 28, 2019·Journal of Cachexia, Sarcopenia and Muscle·Maria Carmela FilomenaMarie-Louise Bang
Mar 27, 2020·Scientific Reports·Andrea Cerquone PerpetuiniGianni Cesareni
Sep 29, 2020·Frontiers in Physiology·Brandon N VanderVeenJames A Carson
Jul 6, 2021·Frontiers in Physiology·Caroline BarbéJean-Paul Thissen
Aug 26, 2021·Journal of Cachexia, Sarcopenia and Muscle·Yuancheng MaoByung-Hyun Park

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Methods Mentioned

BETA
GTPases
GTPase
mechanical dissociation
transfection
Assay
Profiler
dissection
PCR

Software Mentioned

ImageJ
GraphPad
GraphPad Prism
Photoshop
Cell Profiler

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