IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma

被引:49
作者
Gao, Ling [1 ,2 ]
Wang, Xiaolong [1 ]
Wang, Xiaofei [2 ]
Zhang, Linmei [1 ]
Qiang, Cui [1 ]
Chang, Su'e [2 ]
Ren, Wenhao [1 ]
Li, Shaoming [1 ]
Yang, Yang [2 ]
Tong, Dongdong [2 ]
Chen, Cheng [1 ]
Li, Zongfang [3 ]
Song, Tusheng [2 ]
Zhi, Keqian [1 ]
Huang, Chen [2 ]
机构
[1] Xi An Jiao Tong Univ, Coll Med, Dept Oral Maxillofacial Surg, Stomatol Hosp, Xian 710049, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Coll Med, Key Lab Environm & Genes Related Dis, Xian 710049, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Sch Med, Dept Gen Surg, Affiliated Hosp 2, Xian 710049, Shaanxi, Peoples R China
关键词
oral squamous cell carcinoma; IGF-1R; IRS-2; let-7b; proliferation; CANCER; MICRORNA; RECEPTOR; GROWTH; ACTIVATION; ERK; PHOSPHORYLATION; INTEGRATION; INHIBITION; EXPRESSION;
D O I
10.18632/oncotarget.1812
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Insulin-like growth factor (IGF) signaling is involved in oral squamous cell carcinoma (OSCC), but IGF-1 receptor (IGF-1R)-mediated intricate regulatory networks among molecular interactions and signalling path ways in OSCC remain unclear. Here, we found that overexpression of IGF-1R and insulin receptor substrate-2 (IRS-2) was negatively associated with histological differentiation. IGF signaling stimulated OSCC cell growth. Conversely, overexpression of let-7b inhibited proliferation and colony formation and triggered S/G2 cell cycle arrest by targeting IGF-1R and IRS-2 through the Akt pathway. Also, the inverse relationship between expression of let-7b and IGF-1R/IRS-2 was confirmed in OSCC tumor xenografts and clinical specimens. Furthermore, by activating ERK1/2, IGF-1R transcriptionally upregulated IRS-2. Our results indicate that let-7b/IGF-1R-mediated crosstalk between IRS-2/Akt and MAPK is involved in OSCC and is a potential therapeutic target for therapy.
引用
收藏
页码:2562 / 2574
页数:13
相关论文
共 51 条
[1]
PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells [J].
Aksamitiene, Edita ;
Kholodenko, Boris N. ;
Kolch, Walter ;
Hoek, Jan B. ;
Kiyatkin, Anatoly .
CELLULAR SIGNALLING, 2010, 22 (09) :1369-1378
[2]
Alajez NM, 2012, ONCOTARGET, V3, P1641
[3]
Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer [J].
Ang, K. Kian ;
Harris, Jonathan ;
Wheeler, Richard ;
Weber, Randal ;
Rosenthal, David I. ;
Nguyen-Tan, Phuc Felix ;
Westra, William H. ;
Chung, Christine H. ;
Jordan, Richard C. ;
Lu, Charles ;
Kim, Harold ;
Axelrod, Rita ;
Silverman, C. Craig ;
Redmond, Kevin P. ;
Gillison, Maura L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (01) :24-35
[4]
Enhanced Efficacy of IGF1R Inhibition in Pediatric Glioblastoma by Combinatorial Targeting of PDGFRα/β [J].
Bielen, Aleksandra ;
Perryman, Lara ;
Box, Gary M. ;
Valenti, Melanie ;
Brandon, Alexis de Haven ;
Martins, Vanessa ;
Jury, Alexa ;
Popov, Sergey ;
Gowan, Sharon ;
Jeay, Sebastien ;
Raynaud, Florence I. ;
Hofmann, Francesco ;
Hargrave, Darren ;
Eccles, Suzanne A. ;
Jones, Chris .
MOLECULAR CANCER THERAPEUTICS, 2011, 10 (08) :1407-1418
[5]
Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells [J].
Byron, S. A. ;
Horwitz, K. B. ;
Richer, J. K. ;
Lange, C. A. ;
Zhang, X. ;
Yee, D. .
BRITISH JOURNAL OF CANCER, 2006, 95 (09) :1220-1228
[6]
MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias [J].
Calin, GA ;
Liu, CG ;
Sevignani, C ;
Ferracin, M ;
Felli, N ;
Dumitru, CD ;
Shimizu, M ;
Cimmino, A ;
Zupo, S ;
Dono, M ;
Dell'Aquila, ML ;
Alder, H ;
Rassenti, L ;
Kipps, TJ ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) :11755-11760
[7]
MicroRNA detection and target prediction: Integration of computational and experimental approaches [J].
Chaudhuri, Keya ;
Chatterjee, Raghunath .
DNA AND CELL BIOLOGY, 2007, 26 (05) :321-337
[8]
The Type 1 Insulin-Like Growth Factor Receptor Pathway [J].
Chitnis, Meenali M. ;
Yuen, John S. P. ;
Protheroe, Andrew S. ;
Pollak, Michael ;
Macaulay, Valentine M. .
CLINICAL CANCER RESEARCH, 2008, 14 (20) :6364-6370
[9]
IGF-1R is overexpressed in poor-prognostic subtypes of multiple myeloma [J].
Chng, WJ ;
Gualberto, A ;
Fonseca, R .
LEUKEMIA, 2006, 20 (01) :174-176
[10]
Molecular origins of cancer: Oncogenes and cancer [J].
Croce, Carlo M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (05) :502-511