LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFRβ signaling
Authors: Ting Lei
Qungen Xiao
Dongsheng Guo
Heping Wang
Minhai Dong
Weifeng Zong
Fangling Cheng
Kang Wu
Ruifan Xie
Feng Mao
Baofeng Wang
Journal: International Journal of Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: LRIG gene family; tumor suppressor; LRIG2; epidermal growth factor receptor; EGFR signaling
Affiliations: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Abstract:  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 β (PDGFRβ) signaling, another common oncogenic RTK signaling pathway in GBM. First, the expression levels of endogenous LRIG2 and PDGFRβ were found to vary notably in human GBM, and the LRIG2 expression level was positively correlated with the expression level of PDGFRβ. 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 PDGFRβ signaling‑mediated cell cycle progression. Mechanistically, LRIG2 has the ability to physically interact with PDGFRβ, promoting the total expression and the activation of PDGFRβ, 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 PDGFRβ 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. 

Retracted: No

PubPeer comments:
 This paper is one of a set of four papers by shared authors that appear to reuse images of fungi. The four papers are: * Abhinay Thakur , Sanehdeep Kaur , Amarjeet Kaur Varinder Singh - Detrimental effects of endophytic fungus Nigrospora sp. on survival and development of Spodoptera litura - Biocontrol Science and Technology, 22:2, 151-161 - DOI: 10.1080 09583157.2011.646952 - https: pubpeer.com publications A61B13B97339ADC0AB411B309D44A3 * Abhinay Thakur Varinder Singh Amarjeet Kaur Sanehdeep Kaur - Insecticidal potential of an endophytic fungus, Cladosporium uredinicola, against Spodoptera litura - Phytoparasitica (2013) 41:373u2013382 - DOI: 10.1007 s12600-013-0298-9 - https: pubpeer.com publications E864E797056589293FB890CCE826F4 * Abhinay Thakur, Sanehdeep Kaur, Amarjeet Kaur, Varinder Singh - Enhanced Resistance to Spodoptera litura in Endophyte Infected Cauliflower Plants - Environ Entomol . 2013 Apr;42(2):240-6 - DOI: 10.1603 EN12001 - https: pubpeer.com publications 6A3333893F38F4EF21A3685F9520FC * Varinder Singh, Jyoti Bhagat, Bhupinder Singh Chadha, Rajesh Kumari Manhas and Amarjeet Kaur - Acetylcholinestersae [*sic*} inhibitory potential of endophytic fungi inhabiting three Indian medicinal plants - Int J Pharm 2016; 6(1): 129-136 - No DOI In each paper, the photos are illustrations of the fungi being isolated from plants, and they might represent the same experiment, but it is unexpected to publish the same experiment multiple times, and there is no statement about permission to reuse the image from the previous journal(s). Here are four photos from fungi, in the same order as the four papers above, from left to right. ![file] , 
 This paper is also one of a set of six papers (partially overlapping with the set mentioned in comment #1) that appear to reuse images of Spodoptera litura moths, even though they represent different experimental treatment. Brought to my attention by a reader. Here are the images, marked with boxes of the same color. First row from left to right: * Abhinay Thakur , Sanehdeep Kaur , Amarjeet Kaur Varinder Singh - Detrimental effects of endophytic fungus Nigrospora sp. on survival and development of Spodoptera litura - Biocontrol Science and Technology, 22:2, 151-161 - DOI: 10.1080 09583157.2011.646952 - https: pubpeer.com publications A61B13B97339ADC0AB411B309D44A3 * Abhinay Thakur Varinder Singh Amarjeet Kaur Sanehdeep Kaur - Insecticidal potential of an endophytic fungus, Cladosporium uredinicola, against Spodoptera litura - Phytoparasitica (2013) 41:373u2013382 - DOI: 10.1007 s12600-013-0298-9 - https: pubpeer.com publications E864E797056589293FB890CCE826F4 * Abhinay Thakur, Sanehdeep Kaur, Amarjeet Kaur, Varinder Singh - Enhanced Resistance to Spodoptera litura in Endophyte Infected Cauliflower Plants - Environ Entomol . 2013 Apr;42(2):240-6 - DOI: 10.1603 EN12001 - https: pubpeer.com publications 6A3333893F38F4EF21A3685F9520FC Second row from left to right: * Sanehdeep Kaur, Harminder Preet Kaur, Kirandeep Kaur and Amarjeet Kaur - Effect of different concentrations of Beauveria bassiana on development and reproductive potential of Spodoptera litura (Fabricius) - Journal of Biopesticides, 4 (2): 161-168 (2011) - No DOI * Abhinay Thakur, Prince Dhammi, Harvinder Singh Saini, Sanehdeep Kaur - Pathogenicity of bacteria isolated from gut of Spodoptera litura (Lepidoptera: Noctuidae) and fitness costs of insect associated with consumption of bacteria - Journal of Invertebrate Pathology (2015) - DOI: 10.1016 j.jip.2015.02.007 - https: pubpeer.com publications 295A60A56635D1F3FFB5AD62A7AEC4 * Mandeep Kaur, Rakesh Kumar, Deep Patel Upendrabhai, Inder Pal Singh, Sanehdeep Kaur - Impact of sesquiterpenes from Inula racemosa (Asteraceae) on growth, development and nutrition of Spodoptera litura (Lepidoptera: Noctuidae) - Pest Management Science (2017) - DOI: 10.1002 ps.4429 - https: pubpeer.com publications 72A34502A6CF8F06332928D41EDB1B ![file] ![file] ,