Details

Autor(en) / Beteiligte

• Xiao, Qungen
• Dong, Minghai
• Cheng, Fangling
• Mao, Feng
• Zong, Weifeng
• Wu, Kang
• Wang, Heping
• Xie, Ruifan
• Wang, Baofeng
• Lei, Ting
• Guo, Dongsheng

Titel

LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFR[beta] signaling

Ist Teil von

• International journal of oncology, 2018-09, Vol.53 (3), p.1069

Ort / Verlag

Spandidos Publications

Erscheinungsjahr

2018

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• The leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family, comprising LRIG1, 2 and 3, encodes integral membrane proteins. It has been well established that LRIG1 negatively regulates multiple growth factor signaling pathways and is considered to be a tumor suppressor; however, the biological functions of LRIG2 remain largely unexplored. It was previously demonstrated that LRIG2 positively regulates epidermal growth factor receptor (EGFR) signaling, the most common aberrant receptor tyrosine kinase (RTK) signaling in glioblastoma multiforme (GBM), which promotes GBM growth. In the present study, the effect of LRIG2 on the proliferation of GBM cells was further addressed, as well as the possible mechanisms underlying the regulatory effect of LRIG2 on platelet-derived growth factor receptor [beta] (PDGFR[beta]) signaling, another common oncogenic RTK signaling pathway in GBM. First, the expression levels of endogenous LRIG2 and PDGFR[beta] were found to vary notably in human GBM, and the LRIG2 expression level was positively correlated with the expression level of PDGFR[beta]. Furthermore, to the best of our knowledge, this is the first study to demonstrate that LRIG2 promoted the PDGF-BB-induced proliferation of GBM cells in vitro and in vivo through regulating the PDGFR[beta] signaling-mediated cell cycle progression. Mechanistically, LRIG2 has the ability to physically interact with PDGFR[beta], promoting the total expression and the activation of PDGFR[beta], and enhancing its downstream signaling pathways of Akt and signal transducer and activator of transcription 3 and the effectors of key regulators of cell cycle progression, resulting in increased GBM cell proliferation. Collectively, these data indicated that LRIG2 may serve as a tumor promoter gene in gliomagenesis by positively regulating PDGFR[beta] signaling, another important oncogenic RTK signaling pathway, in addition to the previously reported EGFR signaling in GBM modulated by LRIG2, and validated LRIG2 as a promising therapeutic target for the treatment of GBM characterized by multiple aberrant RTK signaling. Abbreviations: GMB, glioblastoma multiforme; LRIG, leucine-rich repeats and immunoglobulin-like domains; RTK, receptor tyrosine kinase; PDGFR, platelet-derived growth factor receptor; Stat3, signal transducer and activator of transcription 3 Key words: leucine-rich repeats and immunoglobulin-like domains, platelet-derived growth factor receptor [beta], glioblastoma, proliferation, cell cycle