LGR5 is a Proneural Factor and is Regulated by OLIG2 in Glioma Stem-Like Cells

被引：13

作者：

Mao, Xing-gang ^{[1
,2
]}

Song, Shao-Jun ^{[2
]}

Xue, Xiao-yan ^{[3
]}

Yan, Ming ^{[4
]}

Wang, Liang ^{[5
]}

Lin, Wei ^{[1
]}

Guo, Geng ^{[6
]}

Zhang, Xiang ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Neurosurg, Xian 710032, Shaanxi Provinc, Peoples R China

[2] PLA 254 Hosp, Dept Neurosurg, Tianjin, Peoples R China

[3] Fourth Mil Med Univ, Sch Pharm, Dept Pharmacol, Xian 710032, Shaanxi Provinc, Peoples R China

[4] Fourth Mil Med Univ, Xijing Hosp, Dept Orthopaed Surg, Xian 710032, Shaanxi Provinc, Peoples R China

[5] Fourth Mil Med Univ, Tangdu Hosp, Dept Neurosurg, Xian 710032, Shaanxi Provinc, Peoples R China

[6] Shanxi Med Univ, Hosp 1, Dept Neurosurg, Taiyuan, Shanxi Province, Peoples R China

来源：

CELLULAR AND MOLECULAR NEUROBIOLOGY | 2013年 / 33卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Cancer stem cell; Glioblastoma multiforme; Bioinformatics; WNT; Neuronal differentiation; PROTEIN-COUPLED RECEPTOR; TUMOR-INITIATING CELLS; GENE-EXPRESSION; CANCER-CELLS; POSTMITOTIC NEURONS; HUMAN GLIOBLASTOMA; NERVOUS-SYSTEM; BREAST-CANCER; HUMAN BRAIN; IN-VITRO;

D O I：

10.1007/s10571-013-9951-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs. Furthermore, LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and GSC maintenance. Biological experiments in GSC cells validated the bioinformatics analysis results and revealed that LGR5 regulated the tumor sphere formation capacity, an important stem cell property for GSCs. Therefore, LGR5 expression may be functionally correlated with the neurogenic competence, and be regulated by OLIG2 in GSCs.

引用

页码：851 / 865

页数：15

共 75 条

[1] IN SITU HYBRIDIZATION REVEALS DEVELOPMENTAL REGULATION OF ErbB1-4 mRNA EXPRESSION IN MOUSE MIDBRAIN: IMPLICATION OF ErbB RECEPTORS FOR DOPAMINERGIC NEURONS [J].

Abe, Y. ;

Namba, H. ;

Zheng, Y. ;

Nawa, H. .

NEUROSCIENCE, 2009, 161 (01) :95-110

[2] Paired overexpression of ErbB3 and Sox10 in pilocytic astrocytoma [J].

Addo-Yobo, Steven O. ;

Straessle, Jennifer ;

Anwar, Adil ;

Donson, Andrew M. ;

Kleinschmidt-DeMasters, B. K. ;

Foreman, Nicholas K. .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2006, 65 (08) :769-775

[3] Olig2-Induced Neural Stem Cell Differentiation Involves Downregulation of Wnt Signaling and Induction of Dickkopf-1 Expression [J].

Ahn, Sung-Min ;

Byun, Kyunghee ;

Kim, Deokhoon ;

Lee, Kiyoung ;

Yoo, Jong Shin ;

Kim, Seung U. ;

Jho, Eek-hoon ;

Simpson, Richard J. ;

Lee, Bonghee .

PLOS ONE, 2008, 3 (12)

[4] Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas [J].

Bannykh, SI ;

Stolt, CC ;

Kim, J ;

Perry, A ;

Wegner, M .

JOURNAL OF NEURO-ONCOLOGY, 2006, 76 (02) :115-127

[5] Targeting cancer stem cells through L1CAM suppresses glioma growth [J].

Bao, Shideng ;

Wu, Qiulian ;

Li, Zhizhong ;

Sathornsumetee, Sith ;

Wang, Hui ;

McLendon, Roger E. ;

Hjehneland, Anita B. ;

Rich, Jeremy N. .

CANCER RESEARCH, 2008, 68 (15) :6043-6048

[6] Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].

Barker, Nick ;

van Es, Johan H. ;

Kuipers, Jeroen ;

Kujala, Pekka ;

van den Born, Maaike ;

Cozijnsen, Miranda ;

Haegebarth, Andrea ;

Korving, Jeroen ;

Begthel, Harry ;

Peters, Peter J. ;

Clevers, Hans .

NATURE, 2007, 449 (7165) :1003-U1

[7] Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma [J].

Barrett, Lindy E. ;

Granot, Zvi ;

Coker, Courtney ;

Lavarone, Antonio ;

Hambardzumyan, Dolores ;

Holland, Eric C. ;

Hyung-song Nam ;

Benezra, Robert .

CANCER CELL, 2012, 21 (01) :11-24

[8] Sertad1 Plays an Essential Role in Developmental and Pathological Neuron Death [J].

Biswas, Subhas C. ;

Zhang, Yi ;

Iyirhiaro, Grace ;

Willett, Ryan T. ;

Gonzalez, Yasmilde Rodriguez ;

Cregan, Sean P. ;

Slack, Ruth S. ;

Park, David S. ;

Greene, Lloyd A. .

JOURNAL OF NEUROSCIENCE, 2010, 30 (11) :3973-3982

[9] Hoxd1 is expressed by oligodendroglial cells and binds to a region of the human myelin oligodendrocyte glycoprotein promoter in vitro [J].

Booth, Jayaum ;

Nicolay, Danette J. ;

Doucette, J. Ronald ;

Nazarali, Adil J. .

CELLULAR AND MOLECULAR NEUROBIOLOGY, 2007, 27 (05) :641-650

[10] Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system [J].

Brinkmann, Bastian G. ;

Agarwal, Amit ;

Sereda, Michael W. ;

Garratt, Alistair N. ;

Mueller, Thomas ;

Wende, Hagen ;

Stassart, Ruth M. ;

Nawaz, Schanila ;

Humml, Christian ;

Velanac, Viktorija ;

Radyushkin, Konstantin ;

Goebbels, Sandra ;

Fischer, Tobias M. ;

Franklin, Robin J. ;

Lai, Cary ;

Ehrenreich, Hannelore ;

Birchmeier, Carmen ;

Schwab, Markus H. ;

Nave, Klaus Armin .

NEURON, 2008, 59 (04) :581-595

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