GCIP functions as a tumor suppressor in non-small cell lung cancer by suppressing Id1-mediated tumor promotion
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Kuan-yu Chen1, Chao-chung Chen2, Yau-lin Tseng4, Yi-chien Chang4 and Ming-Chung Chang1,3
1 Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan
2 Department of Biotechnology, College of Medicine and Nursing, Hung Kuang University, Taichung, Tainan
3 Department of Nutrition, College of Medicine and Nursing, Hung Kuang University, Taichung, Tainan
4 Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan
Ming-chung Chang, email:
Keywords: GCIP, NSCLC, Id1, tumor suppressor
Received: April 4, 2014 Accepted: June 6, 2014 Published: June 7, 2014
Grap2 and cyclin D1 interacting protein (GCIP) has been recognized as a putative tumor suppressor, but the molecular mechanisms underlying its anti-tumor properties remain undefined. Here, we report that GCIP is frequently downregulated in non-small cell lung cancer (NSCLC) tissues. Binding assays indicated that inhibitor of DNA binding/differentiation 1 (Id1) interacts with GCIP in the nucleus. Ectopic GCIP expression in the highly invasive NSCLC cell line, H1299, inhibited proliferation, colony formation, invasion and migration, and increased susceptibility to anticancer drugs. Conversely, silencing GCIP expression in the minimally invasive NSCLS cell line, A549, increased proliferation, colony formation, invasion, and migration in vitro, and increased survival and resistance to anticancer drugs. GCIP also suppresses tumorigenicity of NSCLC cells in vivo and GCIP suppresses NSCLC progression is mediated in part by interfering with Id1 signaling, which was confirmed in conditionally induced stable cell lines. In addition, GCIP downregulates the expression of Id1, and GCIP and Id1 are inversely expressed in NSCLC cell lines and specimens. Taken together, these results suggest that GCIP is a potential tumor suppressor in NSCLC and that suppression of Id1-mediated oncogenic properties may be a key mechanism by which GCIP can potently suppress NSCLC tumor progression.
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