Tags

Type your tag names separated by a space and hit enter

Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness.
Carcinogenesis. 2014 Oct; 35(10):2382-92.C

Abstract

Rhabdomyosarcoma is a muscle-derived malignant tumor mainly affecting children. The most frequent variant, embryonal rhabdomyosarcoma (ERMS) is characterized by overexpression of the transcription factor, PAX7 which prevents ERMS cells from exiting the cell cycle and terminally differentiating. However, a role for PAX7 in the invasive properties of ERMS cells has not been investigated in detail thus far. Here we show that ectopic expression of receptor for advanced glycation end-products (RAGE) in human ERMS cells results in the activation of a RAGE/myogenin axis which downregulates PAX7 by transcriptional and post-translational mechanisms, as in normal myoblasts, and reduces metastasis formation. High PAX7 sustains migration and invasiveness in ERMS cells by upregulating EPHA3 and EFNA1 and downregulating NCAM1 thus decreasing the neural cell adhesion molecule (NCAM)/polysialylated-NCAM ratio. Microarray gene expression analysis shows that compared with the RAGE(-ve) TE671/WT cells and similarly to primary human myoblasts, TE671/RAGE cells show upregulation of genes involved in muscle differentiation and cell adhesion, and downregulation of cell migration related and major histocompatibility complex class I genes. Our data reveal a link between PAX7 and metastasis occurrence in ERMSs, and support a role for the RAGE/myogenin axis in metastasis suppression. Thus, low RAGE expression in ERMS primary tumors may be predictive of metastatic behavior.

Authors+Show Affiliations

Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy, Interuniversity Institute of Myology (IIM), Italy and.Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy, Interuniversity Institute of Myology (IIM), Italy and.Interuniversity Institute of Myology (IIM), Italy and Department of Neuroscience and Imaging, CeSI, University G. d'Annunzio Chieti-Pescara, 66013 Chieti, Italy.Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy, Interuniversity Institute of Myology (IIM), Italy and.Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy, Interuniversity Institute of Myology (IIM), Italy and guglielmo.sorci@unipg.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25123133

Citation

Chiappalupi, Sara, et al. "Defective RAGE Activity in Embryonal Rhabdomyosarcoma Cells Results in High PAX7 Levels That Sustain Migration and Invasiveness." Carcinogenesis, vol. 35, no. 10, 2014, pp. 2382-92.
Chiappalupi S, Riuzzi F, Fulle S, et al. Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness. Carcinogenesis. 2014;35(10):2382-92.
Chiappalupi, S., Riuzzi, F., Fulle, S., Donato, R., & Sorci, G. (2014). Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness. Carcinogenesis, 35(10), 2382-92. https://doi.org/10.1093/carcin/bgu176
Chiappalupi S, et al. Defective RAGE Activity in Embryonal Rhabdomyosarcoma Cells Results in High PAX7 Levels That Sustain Migration and Invasiveness. Carcinogenesis. 2014;35(10):2382-92. PubMed PMID: 25123133.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness. AU - Chiappalupi,Sara, AU - Riuzzi,Francesca, AU - Fulle,Stefania, AU - Donato,Rosario, AU - Sorci,Guglielmo, Y1 - 2014/08/14/ PY - 2014/8/16/entrez PY - 2014/8/16/pubmed PY - 2015/5/12/medline SP - 2382 EP - 92 JF - Carcinogenesis JO - Carcinogenesis VL - 35 IS - 10 N2 - Rhabdomyosarcoma is a muscle-derived malignant tumor mainly affecting children. The most frequent variant, embryonal rhabdomyosarcoma (ERMS) is characterized by overexpression of the transcription factor, PAX7 which prevents ERMS cells from exiting the cell cycle and terminally differentiating. However, a role for PAX7 in the invasive properties of ERMS cells has not been investigated in detail thus far. Here we show that ectopic expression of receptor for advanced glycation end-products (RAGE) in human ERMS cells results in the activation of a RAGE/myogenin axis which downregulates PAX7 by transcriptional and post-translational mechanisms, as in normal myoblasts, and reduces metastasis formation. High PAX7 sustains migration and invasiveness in ERMS cells by upregulating EPHA3 and EFNA1 and downregulating NCAM1 thus decreasing the neural cell adhesion molecule (NCAM)/polysialylated-NCAM ratio. Microarray gene expression analysis shows that compared with the RAGE(-ve) TE671/WT cells and similarly to primary human myoblasts, TE671/RAGE cells show upregulation of genes involved in muscle differentiation and cell adhesion, and downregulation of cell migration related and major histocompatibility complex class I genes. Our data reveal a link between PAX7 and metastasis occurrence in ERMSs, and support a role for the RAGE/myogenin axis in metastasis suppression. Thus, low RAGE expression in ERMS primary tumors may be predictive of metastatic behavior. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/25123133/Defective_RAGE_activity_in_embryonal_rhabdomyosarcoma_cells_results_in_high_PAX7_levels_that_sustain_migration_and_invasiveness_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgu176 DB - PRIME DP - Unbound Medicine ER -