Biglycan Regulates MG63 Osteosarcoma Cell Growth Through a LPR6/β-Catenin/IGFR-IR Signaling Axis.

作者: John Aggelidakis , Aikaterini Berdiaki , Dragana Nikitovic , Antonis Papoutsidakis , Dionysios J. Papachristou

DOI: 10.3389/FONC.2018.00470

关键词: LRP6Cell growthWnt signaling pathwayCateninDownregulation and upregulationBiglycanMolecular biologyReceptorInsulin-like growth factor 1 receptorChemistry

摘要: Biglycan, a small leucine rich proteoglycan (SLRP), is an important participant in bone homeostasis and development as well pathology. In the present study biglycan was identified positive regulator of MG63 osteosarcoma cell growth (p ≤ 0.001). IGF-I shown to increase expression 0.01), whereas biglycan-deficiency attenuated significantly both basal induced proliferation cells 0.001; p 0.01, respectively). These effects were executed through IGF-IR receptor whose activation strongly 0.01) biglycan-deficient cells. previously regulate Wnt/β-catenin pathway, demonstrated induce significant β-catenin protein evident at cytoplasmic membrane nucleus fractions 0.05). As by immunofluorescence, attributed co-localization with Wnt co-receptor low-density lipoprotein receptor-related 6 (LRP6) resulting degradation. Furthermore, applying anti-β-catenin anti-pIGF-IR antibodies MG-63 interaction between these molecules that increased upon exogenous treatment. parallel, downregulation inhibited IGF-I-dependent ERK1/2 activation, summary, we report novel mechanism where LRP6/β-catenin/IGF-IR signaling axis enhances growth.

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