The small GTPase Rac1 is involved in the maintenance of stemness and malignancies in glioma stem-like cells

被引：45

作者：

Yoon, Chang-Hwan ^{[1
]}

Hyun, Kyung-Hwan ^{[1
]}

Kim, Rae-Kwon ^{[1
]}

Lee, Hyejin ^{[1
]}

Lim, Eun-Jung ^{[1
]}

Chung, Hee-Yong ^{[2
]}

An, Sungkwan ^{[3
]}

Park, Myung-Jin ^{[4
]}

Suh, Yongjoon ^{[1
]}

Kim, Min-Jung ^{[1
,5
]}

Lee, Su-Jae ^{[1
]}

机构：

[1] Hanyang Univ, Dept Chem, Res Inst Nat Sci, Seoul 133791, South Korea

[2] Hanyang Univ, Dept Med, Seoul 133791, South Korea

[3] Konkuk Univ, Dept Microbiol Engn, Seoul 143701, South Korea

[4] Korea Inst Radiol & Med Sci, Div Radiat Canc Biol, Seoul 139706, South Korea

[5] Korea Atom Energy Res Inst, Environm Radiat Res Grp, Dept Radiat Biol, Taejon, South Korea

来源：

FEBS LETTERS | 2011年 / 585卷 / 14期

关键词：

Rac1; Glioma stem-like cells; Migration and invasion; Radiation resistance; HUMAN BREAST-CANCER; RHO-GTPASES; ACTIVATION; PROGRESSION; OVEREXPRESSION; GLIOBLASTOMA; EXPRESSION; RESISTANCE; MIGRATION; INVASION;

D O I：

10.1016/j.febslet.2011.05.070

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A subpopulation of cancer cells with stem cell properties is responsible for tumor formation, maintenance, and malignant progression; however, the molecular mechanisms underlying the maintenance of cancer stem-like cell properties have remained unclear. Here, we show that the Rho family GTPase Rac1 is involved in the glioma stem-like cell (GSLC) maintenance and tumorigenicity in human glioma. The Rac1-Pak signaling was markedly activated in GSLCs. Knockdown of Rac1 caused reduction of expression of GSLC markers, self-renewal-related proteins and neurosphere formation. Moreover, down-regulation of Rac1 suppressed the migration, invasion, and malignant transformation in GSLCs. Furthermore, inhibition of Rac1 enhanced radiation sensitivity of GSLCs. These results indicate that the small GTPase Rac1 is involved in the maintenance of stemness and malignancies in GSLCs. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：2331 / 2338

页数：8

共 37 条

[1] Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor [J].

Bao, Shideng ;

Wu, Qiulian ;

Sathornsumetee, Sith ;

Hao, Yueling ;

Li, Zhizhong ;

Hjelmeland, Anita B. ;

Shi, Oing ;

McLendon, Roger E. ;

Bigner, Darell D. ;

Rich, Jeremy N. .

CANCER RESEARCH, 2006, 66 (16) :7843-7848

[2] Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells [J].

Baugher, PJ ;

Krishnamoorthy, L ;

Price, JE ;

Dharmawardhane, SF .

BREAST CANCER RESEARCH, 2005, 7 (06) :R965-R974

[3] SUMOylation of the GTPase Rac1 is required for optimal cell migration [J].

Castillo-Lluva, Sonia ;

Tatham, Michael H. ;

Jones, Richard C. ;

Jaffray, Ellis G. ;

Edmondson, Ricky D. ;

Hay, Ronald T. ;

Malliri, Angeliki .

NATURE CELL BIOLOGY, 2010, 12 (11) :1078-U70

[4] Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion [J].

Chan, AY ;

Coniglio, SJ ;

Chuang, YY ;

Michaelson, D ;

Knaus, UG ;

Philips, MR ;

Symons, M .

ONCOGENE, 2005, 24 (53) :7821-7829

[5] Role of synaptojanin 2 in glioma cell migration and invasion [J].

Chuang, YY ;

Tran, NL ;

Rusk, N ;

Nakada, M ;

Berens, ME ;

Symons, M .

CANCER RESEARCH, 2004, 64 (22) :8271-8275

[6] Rho GTPase expression in tumourigenesis:: evidence for a significant link [J].

del Pulgar, TG ;

Benitah, SA ;

Valerón, PF ;

Espina, C ;

Lacal, JC .

BIOESSAYS, 2005, 27 (06) :602-613

[7] A critical role for Rac1 in tumor progression of human colorectal adenocarcinoma cells [J].

Espina, Carolina ;

Virtudes Cespedes, Maria ;

Angel Garcia-Cabezas, Miguel ;

Teresa Gomez del Pulgar, Maria ;

Boluda, Alicia ;

Garcia Oroz, Lourdes ;

Cejas, Paloma ;

Nistal, Manuel ;

Mangues, Ramon ;

Carlos Lacal, Juan .

AMERICAN JOURNAL OF PATHOLOGY, 2008, 172 (01) :156-166

[8] DNA Repair and Resistance of Gliomas to Chemotherapy and Radiotherapy [J].

Frosina, Guido .

MOLECULAR CANCER RESEARCH, 2009, 7 (07) :989-999

[9]

Grudzien P, 2010, ANTICANCER RES, V30, P3853

[10] Mechanisms of Stem Cell Self-Renewal [J].

He, Shenghui ;

Nakada, Daisuke ;

Morrison, Sean J. .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2009, 25 :377-406

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