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Signaling pathways in Rhabdomyosarcoma invasion and metastasis

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Abstract

Rhabdomyosarcoma (RMS) is an aggressive childhood mesenchymal tumor with two major molecular and histopathologic subtypes: fusion-positive (FP)RMS, characterized by the PAX3-FOXO1 fusion protein and largely of alveolar histology, and fusion-negative (FN)RMS, the majority of which exhibit embryonal tumor histology. Metastatic disease continues to be associated with poor overall survival despite intensive treatment strategies. Studies on RMS biology have provided some insight into autocrine as well as paracrine signaling pathways that contribute to invasion and metastatic propensity. Such pathways include those driven by the PAX3-FOXO1 fusion oncoprotein in FPRMS and signaling pathways such as IGF/RAS/MEK/ERK, PI3K/AKT/mTOR, cMET, FGFR4, and PDGFR in both FP and FNRMS. In addition, specific cytoskeletal proteins, G protein coupled receptors, Hedgehog, Notch, Wnt, Hippo, and p53 pathways play a role, as do specific microRNA. Paracrine factors, including secreted proteins and RMS-derived exosomes that carry cargo of protein and miRNA, have also recently emerged as potentially important players in RMS biology. This review summarizes the known factors contributing to RMS invasion and metastasis and their implications on identifying targets for treatment and a better understanding of metastatic RMS.

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  1. Department of Biology, Faculty of Science II, Lebanese University, Fanar, Beirut, Lebanon

    Farah Ramadan, Assil Fahs & Sandra E. Ghayad

  2. Department of Anatomy, Cellular Biology & Physiological Sciences, American University of Beirut, Beirut, Lebanon

    Assil Fahs & Raya Saab

  3. Department of Pediatrics, American University of Beirut Medical Center, Building 56, Riad El Solh Street, Beirut, Lebanon

    Raya Saab

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Ramadan, F., Fahs, A., Ghayad, S.E. et al. Signaling pathways in Rhabdomyosarcoma invasion and metastasis. Cancer Metastasis Rev 39, 287–301 (2020). https://doi.org/10.1007/s10555-020-09860-3

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