A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4

Dwianingsih, Ery Kus; Takeshima, Yasuhiro; Itoh, Kyoko; Yamauchi, Yumiko; Awano, Hiroyuki; Malueka, Rusdy Ghazali; Nishida, Atsushi; M, Ota; Yagi, Minoru; Matsuo, Masafumi

doi:10.1016/j.ymgme.2010.06.016

Cited by 55 publications

(30 citation statements)

References 29 publications

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“…For example, as mentioned above, deficiency in Cav1 protein leads to severe and generalized lipodystrophy (Cao et al, 2008;Kim et al, 2008), whereas mutations in Cav3 lead to the development of several different muscle disease conditions (for a review, see Gazzerro et al, 2010). Cavin-1 mutations are associated with both lipodystrophy and muscle disease (Dwianingsih et al, 2010;Hayashi et al, 2009;Rajab et al, 2010) in agreement with the proposed role of cavin-1 in regulating caveola formation in both muscle and non-muscle tissues. Although the table in the accompanying poster highlights the dystrophic phenotypes directly associated with caveolins and cavin-1 inherited mutations in patients, it should be noted that malfunctioning or changes in the expression levels of these proteins have also been associated with a variety of other diseases both in vitro and in mice models (for a review see Mercier et al, 2009).…”

Section: Perspectivessupporting

confidence: 65%

“…In these models, caveolin exhibits an increased mobility and is associated with a flat plasma membrane . In addition, the loss of caveolae caused by the lack of cavin-1 was associated with degradation of caveolin and with lipid and muscle disorders (Dwianingsih et al, 2010;Hayashi et al, 2009;Hill et al, 2008;Rajab et al, 2010).…”

Section: The Role Of the Cavin Proteins In Caveola Formation And Funcmentioning

confidence: 99%

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Caveolae at a glance

Bastiani

Parton

2010

Journal of Cell Science

185

156

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Section: Perspectivessupporting

confidence: 65%

Section: The Role Of the Cavin Proteins In Caveola Formation And Funcmentioning

confidence: 99%

Caveolae at a glance

Bastiani

Parton

2010

Journal of Cell Science

185

156

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“…For example, deficiency of Cavin-1 in skeletal muscle has been associated with human lipodystrophy, muscular dystrophy and cardiac dysfunction. [79][80][81][82][83][84] In accordance, mice lacking Cavin-1 exhibit a lipodystrophic phenotype 48 as well as an altered metabolic flux among multiple tissues, which suggests a role of Cavin-1 in the coordination of peripheral glucose and fatty-acid storage and utilization. 85 Figure 8 Analysis of the anchorage-independent cell growth in engineered RD cells.…”

Section: Discussionmentioning

confidence: 76%

Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma

Faggi

Chiarelli

Colombi

et al. 2015

Laboratory Investigation

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Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typically found in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in the morphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico and in vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouse RMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. In particular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferation of human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during the myogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human RD and RH30 cells led to impairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independent cell growth in soft agar. While the loss of Cavin-1 did not affect the Cav-1 protein levels in RMS cells, Cav-1 overexpression and knockdown triggered a rise or depletion of Cavin-1 protein levels in RD cells, respectively, in turn reflecting on increased or decreased cell proliferation, migration and anchorage-independent cell growth. Collectively, these data indicate that the interaction between Cavin-1 and Cav-1 underlies the cell growth and migration in myogenic tumors. Rhabdomyosarcoma (RMS) is a childhood soft tissue sarcoma exhibiting broad expression of skeletal muscle markers, 1-3 such as Pax7, MyoD, Myogenin, desmin and muscle-specific actin. 4,5 Cells of origin in RMS may be different muscular and non-muscular cell precursors, 6-8 such as muscle satellite cells (SCs), 9-11 and myoblasts 9,10,12-14 or adipocytes, 15 which are responsible of two major histological subtypes known as embryonal (ERMS) and alveolar (ARMS). The most common ERMS variant arises in children usually o5 years on distinct body sites, such as head, neck and genitourinary regions, while ARMS typically arises in the muscular limb extremities of adolescents and is characterized by poorer prognosis. 16 The genomic landscape causative of ERMS is characterized by a number of genetic lesions and/or somatic mutations that deliberately sustain the activity of different receptors, such as IGF1R, FGFR4 and Patched, 17-21 and related downstream pathways (i.e., RAS/ERK, PI3K/AKT and Sonic Hedgehog signaling). 11,22 In addition, defects in tumor suppressors (i.e., p53), 23 cell cycle regulatory genes (i.e., N-Myc, Rb1) 21,24 and structural proteins involved in muscular integrity (i.e., dystrophin, alpha-sarcoglycan and dysferlin) have been reported. [25][26][27][28][29][30] Conversely, ARMS is dominated by the presence of specific chromosomal translocations leading to expression of the fused Pax3-Foxo1 and Pax7-Foxo1 factors, that driving in a cell cycle manner the transcription of several genes normally restricted to the embryonal development f...

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“…Cavin-1-defi cient patients have a secondary defi ciency of caveolin-1 in adipocytes and therefore present a similar pattern of generalized lipodystrophy with bone marrow preservation, although they retain some mechanical adipose tissue and have vestigial dorsal subcutaneous fat. In addition, cavin-1-defi cient patients manifest features of muscular dystrophy, impaired bone formation, smooth-muscle hypertrophy, and occasional cardiac arrhythmia; this phenotype is probably due to secondary defi ciency of muscle-specifi c caveolin-3 and a more global defect in caveolae ( 24,(30)(31)(32).…”

Section: Neurological Seipinopathiesmentioning

confidence: 99%