Modulations of the calcineurin/NF-AT pathway in skeletal muscle atrophy

Costelli, Paola; Almendro, Vanessa; Figueras, Maria Teresa; Reffo, P.; Penna, Fabio; Aragno, Manuela; Mastrocola, Raffaella; Boccuzzi, Giuseppe; Busquets, Sı́lvia; Bonelli, Gabriella; Soriano, Francisco J. López; Argilés, Josep Μ.; Baccino, Francesco M.

doi:10.1016/j.bbagen.2007.03.003

Cited by 10 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this regard, Guasconi and Puri41 recently proposed that decline in anabolic signals (passive atrophy) and activation of catabolic pathways (active atrophy) may contribute differently to the pathogenesis of muscle atrophy in distinct diseases or unfavorable conditions. Further support to this hypothesis comes from reports showing that skeletal muscle atrophy as occurring in tumor hosts and in diabetic rats is attributable to different mechanisms 46, 77…”

Section: Discussionmentioning

confidence: 96%

Cancer of the esophagus and esophagogastric junction

Rice

Rusch

Ishwaran

et al. 2010

Cancer

394

161

View full text Add to dashboard Cite

request of the AJCC, worldwide data from 3 continents were assembled to develop data-driven, harmonized esophageal staging for the seventh edition of the AJCC/UICC cancer staging manuals. METHODS: All-cause mortality among 4627 patients with esophageal and esophagogastric junction cancer who underwent surgery alone (no preoperative or postoperative adjuvant therapy) was analyzed by using novel random forest methodology to produce stage groups for which survival was monotonically decreasing, distinctive, and homogeneous. RESULTS: For lymph node-negative pN0M0 cancers, risk-adjusted 5-year survival was dominated by pathologic tumor classification (pT) but was modulated by histopathologic cell type, histologic grade, and location. For lymph node-positive, pNþM0 cancers, the number of cancer-positive lymph nodes (a new pN classification) dominated survival. Resulting stage groupings departed from a simple, logical arrangement of TNM. Stage groupings for stage I and II adenocarcinoma were based on pT, pN, and histologic grade; and groupings for squamous cell carcinoma were based on pT, pN, histologic grade, and location. Stage III was similar for histopathologic cell types and was based only on pT and pN. Stage 0 and stage IV, by definition, were categorized as tumor in situ (Tis) (high-grade dysplasia) and pM1, respectively. CONCLUSIONS: The prognosis for patients with esophageal and esophagogastric junction cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade, and cancer location. These features were incorporated into a data-driven staging of these cancers for the seventh edition of the AJCC/UICC cancer staging manuals.

show abstract

Section: Discussionmentioning

confidence: 96%

Cancer of the esophagus and esophagogastric junction

Rice

Rusch

Ishwaran

et al. 2010

Cancer

394

161

View full text Add to dashboard Cite

show abstract

“…Myoblast differentiation was also assessed by immunoblotting for known myogenic differentiation markers. Biochemical differentiation was markedly diminished after PABPN1 knockdown with decreases in myogenin, an early differentiation marker (18), noted at 6 and 24 h in all three cell types ( Fig. 3B).…”

Section: Pabpn1 Is Required For Normal Myoblast Proliferation and Difmentioning

confidence: 91%

Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis

Apponi¹,

Leung

Williams³

et al. 2009

Human Molecular Genetics

108

130

View full text Add to dashboard Cite

The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.

show abstract

“…Further support to this hypothesis comes from reports showing that skeletal muscle atrophy as occurring in tumor hosts and in diabetic rats is attributable to different mechanisms. 46,77…”

Section: Cancer Therapymentioning

confidence: 99%

Muscle atrophy in experimental cancer cachexia: Is the IGF‐1 signaling pathway involved?

Penna

Bonetto

Muscaritoli

et al. 2010

Intl Journal of Cancer

Self Cite

104

View full text Add to dashboard Cite

Skeletal muscle wasting, one of the main features of cancer cachexia, is associated with marked protein hypercatabolism, and has suggested to depend also on impaired IGF-1 signal transduction pathway. To investigate this point, the state of activation of the IGF-1 system has been evaluated both in rats bearing the AH-130 hepatoma and in mice transplanted with the C26 colon adenocarcinoma. In the skeletal muscle of tumor hosts, the levels of phosphorylated (active) Akt, one of the most relevant kinases involved in the IGF-1 signaling pathway, were comparable to controls, or even increased. Accordingly, downstream targets such as GSK3b, p70 S6K and FoxO1 were hyperphosphorylated, while the levels of phosphorylated eIF2awere markedly reduced with respect to controls. In the attempt to force the metabolic balance toward anabolism, IGF-1 was hyperexpressed by gene transfer in the tibialis muscle of the C26 hosts. In healthy animals, IGF-1 overexpression markedly increased both fiber and muscle size. As a positive control, IGF-1 was also overexpressed in the muscle of aged mice. In IGF-1 hyperexpressing muscles the fiber cross-sectional area definitely increased in both young and aged animals, while, by contrast, loss of muscle mass or reduction of fiber size in mice bearing the C26 tumor were not modified. These results demonstrate that muscle wasting in tumor-bearing animals is not associated with downregulation of molecules involved in the anabolic response, and appears inconsistent, at least, with reduced activity of the IGF-1 signaling pathway.Cancer cachexia is a syndrome characterized by loss of body weight, skeletal muscle proteins, depletion of lipid stores, weakness, and perturbations of the hormonal homeostasis.

show abstract

Modulations of the calcineurin/NF-AT pathway in skeletal muscle atrophy

Cited by 10 publications

References 56 publications

Cancer of the esophagus and esophagogastric junction

Cancer of the esophagus and esophagogastric junction

Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis

Muscle atrophy in experimental cancer cachexia: Is the IGF‐1 signaling pathway involved?

Contact Info

Product

Resources

About