Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 13476-13487 |
| Number of pages | 12 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 8 |
| Publication status | Published - 2017 |
Keywords
- Glioblastoma
- Ryk
- Stem cells
- β-catenin
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RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway. / Adamo, A.; Fiore, D.; Martino, F. et al.
In: Oncotarget, Vol. 8, No. 8, 2017, p. 13476-13487.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway
AU - Adamo, A.
AU - Fiore, D.
AU - Martino, F.
AU - Roscigno, G.
AU - Affinito, Alessandra
AU - Donnarumma, E.
AU - Puoti, I.
AU - Vitiani, Lucia Ricci
AU - Pallini, Roberto
AU - Quintavalle, Cristina
AU - Condorelli, G.
N1 - Export Date: 21 March 2017 Correspondence Address: Condorelli, G.; Department of Molecular Medicine and Medical Biotechnology, 'Federico II' University of NaplesItaly; email: gecondor@unina.it References: Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Dirks, P.B., Identification of human brain tumour initiating cells (2004) Nature, 432, pp. 396-401; Visvader, J.E., Cells of origin in cancer (2011) Nature, 469, pp. 314-322; Reya, T., Morrison, S.J., Clarke, M.F., Weissman, I.L., Stem cells, cancer, and cancer stem cells (2001) Nature, 414, pp. 105-111; Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., Dewhirst, M.W., Rich, J.N., Glioma stem cells promote radioresistance by preferential activation of the DNA damage response (2006) Nature, 444, pp. 756-760; Chen, J., Li, Y., Yu, T.S., McKay, R.M., Burns, D.K., Kernie, S.G., Parada, L.F., A restricted cell population propagates glioblastoma growth after chemotherapy (2012) Nature, 488, pp. 522-526; Roscigno, G., Quintavalle, C., Donnarumma, E., Puoti, I., Diaz-Lagares, A., Iaboni, M., Fiore, D., Gaggianesi, M., MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b (2016) Oncotarget, 7, pp. 580-592; Paul, I., Bhattacharya, S., Chatterjee, A., Ghosh, M.K., Current Understanding on EGFR and Wnt/beta-Catenin Signaling in Glioma and Their Possible Crosstalk (2013) Genes Cancer, 4, pp. 427-446; Katoh, M., Katoh, M., WNT signaling pathway and stem cell signaling network (2007) Clin Cancer Res, 13, pp. 4042-4045; Zheng, H., Ying, H., Wiedemeyer, R., Yan, H., Quayle, S.N., Ivanova, E.V., Paik, J.H., Gan, B., PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas (2010) Cancer cell, 17, pp. 497-509; Jin, X., Jeon, H.Y., Joo, K.M., Kim, J.K., Jin, J., Kim, S.H., Kang, B.G., Choi, Y.J., Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation (2011) Cancer Res, 71, pp. 3066-3075; Katso, R.M., Russell, R.B., Ganesan, T.S., Functional analysis of H-Ryk, an atypical member of the receptor tyrosine kinase family (1999) Mol Cell Biol, 19, pp. 6427-6440; Berndt, J.D., Aoyagi, A., Yang, P., Anastas, J.N., Tang, L., Moon, R.T., Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/beta-catenin signaling (2011) J Cell Biol, 194, pp. 737-750; Lu, W., Yamamoto, V., Ortega, B., Baltimore, D., Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth (2004) Cell, 119, pp. 97-108; Lyu, J., Yamamoto, V., Lu, W., Cleavage of the Wnt receptor Ryk regulates neuronal differentiation during cortical neurogenesis (2008) Dev Cell, 15, pp. 773-780; Wang, X.C., Katso, R., Butler, R., Hanby, A.M., Poulsom, R., Jones, T., Sheer, D., Ganesan, T.S., H-RYK, an unusual receptor kinase: isolation and analysis of expression in ovarian cancer (1996) Mol Med, 2, pp. 189-203; Hirano, H., Yonezawa, H., Yunoue, S., Habu, M., Uchida, H., Yoshioka, T., Kishida, S., Hanaya, R., Immunoreactivity of Wnt5a, Fzd2, Fzd6, and Ryk in glioblastoma: evaluative methodology for DAB chromogenic immunostaining (2014) Brain Tumor Pathol, 31, pp. 85-93; Edgar, R., Domrachev, M., Lash, A.E., Gene Expression Omnibus: NCBI gene expression and hybridization array data repository (2002) Nucleic Acids Res, 30, pp. 207-210; Rhodes, D.R., Yu, J., Shanker, K., Deshpande, N., Varambally, R., Ghosh, D., Barrette, T., Chinnaiyan, A.M., ONCOMINE: a cancer microarray database and integrated data-mining platform (2004) Neoplasia, 6, pp. 1-6; Guidoni, L., Ricci-Vitiani, L., Rosi, A., Palma, A., Grande, S., Luciani, A.M., Pelacchi, F., Viti, V., 1H NMR detects different metabolic profiles in glioblastoma stem-like cells (2014) NMR Biomed, 27, pp. 129-145; Hu, Y., Smyth, G.K., ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays (2009) J Immunol Methods, 347, pp. 70-78; Katso, R.M., Manek, S., Biddolph, S., Whittaker, R., Charnock, M.F., Wells, M., Ganesan, T.S., Overexpression of H-Ryk in mouse fibroblasts confers transforming ability in vitro and in vivo: correlation with up-regulation in epithelial ovarian cancer (1999) Cancer Res, 59, pp. 2265-2270; Jackson, M., Hassiotou, F., Nowak, A., Glioblastoma stemlike cells: at the root of tumor recurrence and a therapeutic target (2015) Carcinogenesis, 36, pp. 177-185; Nusse, R., Wnt signaling and stem cell control (2008) Cell Res, 18, pp. 523-527; Chenn, A., Walsh, C.A., Regulation of cerebral cortical size by control of cell cycle exit in neural precursors (2002) Science, 297, pp. 365-369; Zhang, N., Wei, P., Gong, A., Chiu, W.T., Lee, H.T., Colman, H., Huang, H., Yung, W.K., FoxM1 promotes beta-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis (2011) Cancer Cell, 20, pp. 427-442; Marziali, G., Signore, M., Buccarelli, M., Grande, S., Palma, A., Biffoni, M., Rosi, A., Ricci-Vitiani, L., Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome (2016) Sci Rep, 6, p. 21557; Pallini, R., Ricci-Vitiani, L., Banna, G.L., Signore, M., Lombardi, D., Todaro, M., Stassi, G., De Maria, R., Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme (2008) Clin Cancer Res, 14, pp. 8205-8212; Halford, M.M., Macheda, M.L., Parish, C.L., Takano, E.A., Fox, S., Layton, D., Nice, E., Stacker, S.A., A fully human inhibitory monoclonal antibody to the Wnt receptor RYK (2013) Plos One, 8; Quintavalle, C., Mangani, D., Roscigno, G., Romano, G., Diaz-Lagares, A., Iaboni, M., Donnarumma, E., Condorelli, G., MiR-221/222 target the DNA methyltransferase MGMT in glioma cells (2013) Plos One, 8; Iaboni, M., Russo, V., Fontanella, R., Roscigno, G., Fiore, D., Donnarumma, E., Esposito, C.L., Condorelli, G., Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL (2016) Mol Ther Nucleic Acids, 5; Fiore, D., Donnarumma, E., Roscigno, G., Iaboni, M., Russo, V., Affinito, A., Adamo, A., Brunetti, A., miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS (2016) Oncotarget, 7, pp. 19531-19547; Quintavalle, C., Garofalo, M., Zanca, C., Romano, G., Iaboni, M., del Basso De Caro, M., Martinez-Montero, J.C., Condorelli, G., miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPmu (2012) Oncogene, 31, pp. 858-868
PY - 2017
Y1 - 2017
N2 - Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor tyrosine kinase), an atypical tyrosine kinase receptor, is upregulated in samples from GBM patients as well as in GSCs. Ryk overexpression confers stemness properties to GBM cells through the modulation of the canonical Wnt signaling and by promoting the activation of pluripotency-related transcription factor circuitry and neurosphere formation ability. In contrast, siRNA-mediated knockdown of Ryk expression suppresses this stem-like phenotype. Rescue experiments reveal that stemness-promoting activity of Ryk is attributable, at least in part, to β-catenin stabilization. Furthermore, Ryk overexpression improves cell motility and anchorage independent cell growth. Taken together, our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of GSCs and could be a target of novel therapies.
AB - Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor tyrosine kinase), an atypical tyrosine kinase receptor, is upregulated in samples from GBM patients as well as in GSCs. Ryk overexpression confers stemness properties to GBM cells through the modulation of the canonical Wnt signaling and by promoting the activation of pluripotency-related transcription factor circuitry and neurosphere formation ability. In contrast, siRNA-mediated knockdown of Ryk expression suppresses this stem-like phenotype. Rescue experiments reveal that stemness-promoting activity of Ryk is attributable, at least in part, to β-catenin stabilization. Furthermore, Ryk overexpression improves cell motility and anchorage independent cell growth. Taken together, our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of GSCs and could be a target of novel therapies.
KW - Glioblastoma
KW - Ryk
KW - Stem cells
KW - β-catenin
M3 - Article
VL - 8
SP - 13476
EP - 13487
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 8
ER -