p53 family members in myogenic differentiation and rhabdomyosarcoma development

Çam, Hakan; Griesmann, Heidi; Beitzinger, Michaela; Hofmann, Lars; Beinoraviciute-Kellner, Rasa; Sauer, Markus; Hüttinger-Kirchhof, Nicole; Oswald, Claudia; Friedl, Peter; Gattenlöhner, Stefan; Burek, Christof; Rosenwald, Andreas; Stiewe, Thorsten

doi:10.1016/j.ccr.2006.08.024

Cited by 105 publications

(129 citation statements)

References 43 publications

(59 reference statements)

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“…[104][105][106] Interestingly, it has been demonstrated that cancer cells lacking p53 are protected from oxidative stress-induced by serine depletion in the presence of p73, a p53 family member that has the ability to drive serine biosynthesis de novo 107,108 and to increase the pentose phosphate shunt and nucleotide biosynthesis via G6PD. 109,110 Thus, the p73 overexpression detected in various primary RMS samples 111 may have an important role for oxidative stress resistance.…”

Section: Oxidative Stress Pathwaysmentioning

confidence: 99%

Uncovering metabolism in rhabdomyosarcoma

Monti

Fanzani

2016

Cell Cycle

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Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes five different histotypes, with two most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies two major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signalling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the “state of art” of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies

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Section: Oxidative Stress Pathwaysmentioning

confidence: 99%

Uncovering metabolism in rhabdomyosarcoma

Monti

Fanzani

2016

Cell Cycle

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“…We were intrigued by the pathways enriched in p73-bound loci that are associated with muscle function and development (Table S2). It has been reported that p53, p63, and p73 play at least partially redundant roles in myogenic differentiation and rhabdomyosarcoma formation (12). Alteration of the p53 pathway for example, through a dominant-negative isoform of p73, can block skeletal muscle cell differentiation and promote transformation in vitro (12), and Primers flank c-Jun motifs as assessed by sequence analysis for the same genomic loci as in C. PCR product was resolved by acrylamide gel electrophoresis for reactions using the following DNA samples: genomic input ("I"), DNA purified after ChIP with a c-Jun-specific antibody ("J"), and DNA purified after ChIP with a control, nonspecific, isotypematched antibody ("C").…”

Section: Genes Regulated By Mtor and P73 Classify Rhabdomyosarcomamentioning

confidence: 99%

“…We hypothesized that this role could be related to functions of p73 during myogenic differentiation (12). Although the precise cell of origin remains unknown, studies of molecular translocations provide evidence for mesenchymal stem cells (MSCs) as possible cells of origin for ARMS (15).…”

Section: Genes Regulated By Mtor and P73 Classify Rhabdomyosarcomamentioning

confidence: 99%

Differential regulation of the p73 cistrome by mammalian target of rapamycin reveals transcriptional programs of mesenchymal differentiation and tumorigenesis

Rosenbluth

Mays

Jiang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The transcription factor p73 plays critical roles during development and tumorigenesis. It exhibits sequence identity and structural homology with p53, and can engage p53-like tumor-suppressive programs. However, different pathways regulate p53 and p73, and p73 is not mutated in human tumors. Therefore, p73 represents a therapeutic target, and there is a critical need to understand genes and noncoding RNAs regulated by p73 and how they change during treatment regimens. Here, we define the p73 genomic binding profile and demonstrate its modulation by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) and inducer of p73. Rapamycin selectively increased p73 occupancy at a subset of its binding sites. In addition, multiple determinants of p73 binding, activity, and function were evident, and were modulated by mTOR. We generated an mTOR-p73 signature that is enriched for p73 target genes and miRNAs that are involved in mesenchymal differentiation and tumorigenesis, can classify rhabdomyosarcomas by clinical subtype, and can predict patient outcome.p63 | ChIP-on-Chip | stem cell | muscle | consensus binding site

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“…Methylation-induced silencing of the TAp73 promoter has been found in lymphoblastic leukemias and Burkitt lymphomas (Corn et al, 1999;Kawano et al, 1999). The DNp73 and TAp73 isoforms are co-upregulated in primary rhabdomyosarcomas and tumor-derived cell lines, as compared with normal muscle (Cam et al, 2006). DNp73 isoforms are expressed at high levels in many different tumor types and are related to poor prognosis (Buhlmann and Putzer, 2008).…”

Section: Introductionmentioning

confidence: 99%