Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

Zibat, Arne; Missiaglia, Edoardo; Rosenberger, Albert; Pritchard‐Jones, Kathy; Shipley, Janet; Hahn, Heidi; Fulda, Simone

doi:10.1038/onc.2010.368

Cited by 103 publications

(100 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, real-time PCR revealed that SHH, DHH, IHH, PTCH1, SMO, GLI1, GLI2, and ULK3 transcripts were over-expressed in rhabdomyosarcoma cell lines and biopsy specimens. Recently, it has been reported that human rhabdomyosarcoma specimens express SHH, PTCH1, GLI1, and GLI3 (19,20). Their findings are compatible with our real-time PCR results.…”

Section: Discussionsupporting

confidence: 92%

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Kawabata

Ijiri²,

Ishidou³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. The Hedgehog pathway functions as an organizer in embryonic development. Recent studies have shown that mutation of the PTCH1 gene involved in the Hedgehog pathway affects rhabdomyosarcoma development. However, the expression of Hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. In addition, the effect of pharmacological inhibition of the Hedgehog pathway is not known. We investigated the expression of the genes involved in the Hedgehog pathway using human rhabdomyosarcoma cell lines and biopsy specimens. Further, we evaluated the effect of pharmacological inhibition of the Hedgehog pathway using cyclopamine or GANT61 by WST assay, cell proliferation assay and cell death detection assay. Real-time PCR revealed that human rhabdomyosarcoma cell lines and biopsy specimens overexpressed the following genes: Sonic hedgehog, Indian hedgehog, Desert hedgehog, PTCH1, SMO, GLI1, GLI2 and ULK3. Immunohistochemistry revealed that rhabdomyosarcoma cell lines and biopsy specimens expressed SMO and GLI2. Inhibition of SMO by cyclopamine slowed the growth of human rhabdomyosarcoma cell lines. Similarly, inhibition of GLI by GANT61 slowed the growth of human rhabdomyosarcoma cell lines. Inhibition of cell proliferation and apoptotic cell death together prevented the growth of rhabdomyosarcoma cells by cyclopamine and GANT61 treatment. Our findings suggest that pharmacological inhibition of the Hedgehog pathway may be a useful approach for treating rhabdomyosarcoma patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Kawabata

Ijiri²,

Ishidou³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…In rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, HH signaling is preferentially activated in specific subgroups of RMS. [236][237][238][239] Ptch1, Gli1, and Gli3 are expressed at significant higher levels in embryonal RMS than in fusion-gene negative alveolar RMS than in fusion-gene positive alveolar RMS. High expression of Ptch1 significantly correlated with reduced cumulative survival.…”

Section: Stem Cell Pathwaysmentioning

confidence: 98%

“…High expression of Ptch1 significantly correlated with reduced cumulative survival. 238 Betullinic acid possesses anti-tumoral acivity and overcomes resistance by inducing apoptosis in a variety of human cancers. 240 In preclinical study using RMS-13 cells, which is known to display an activate HH pathway caused by DNA amplification of the Gli1 locus, betullinic acid effectively suppressed HH target gene expression.…”

Section: Stem Cell Pathwaysmentioning

confidence: 99%

Novel Therapeutic Targets in Soft Tissue Sarcomas

Chu¹,

Mulder²

2011

Soft Tissue Tumors

View full text Add to dashboard Cite

“…Accordingly, up-regulation of Hh target genes such as GLI1 and PTCH1 has been demonstrated by retrospective analysis of RMS patient samples or in human RMS cell lines [39][40][41][42][43]. Additionally, activation of Hh pathway seems to be specific for fusion negative RMS (NRMS) and significantly identifies patients with poor prognosis [40,41,44,45]. Despite this recognized role of Hh in RMS, the contribution of the ligand-based signaling versus non-canonical pathway activation in sporadic RMS is still unclear.…”

Section: Role Of Hedgehog Pathway In Rmsmentioning

confidence: 99%

Interfering with Hedgehog Pathway: New Avenues for Targeted Therapy in Rhabdomyosarcoma

Manzella¹,

Schäfer

2016

CDT

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) is the most frequent pediatric soft-tissue tumor accounting for about 7% of childhood malignancies. Multimodal therapy is the standard treatment for individuals with RMS but generally fails to cure high-risk group patients and can result in long-term side effects. Therefore, understanding the mechanisms driving RMS might help to find new candidate targets for more specific and effective therapeutic modalities. One of the molecular machineries, which is often deregulated in cancer and specifically involved in the tumorigenesis of RMS, is Hedgehog (Hh) signaling. There is increasing evidence that targeting this developmental pathway may hold promise in future treatment strategies for RMS. In this review, we discuss the contribution of the Hh pathway in RMS, the challenges of inhibiting this embryonic signaling in children with an update on recent preclinical data and ongoing clinical trials.

show abstract

Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

Cited by 103 publications

References 37 publications

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Novel Therapeutic Targets in Soft Tissue Sarcomas

Interfering with Hedgehog Pathway: New Avenues for Targeted Therapy in Rhabdomyosarcoma

Contact Info

Product

Resources

About