title: GCIP functions as a tumor suppressor in non-small cell lung cancer by suppressing Id1-mediated tumor promotion.
abstract: 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.
authors: Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors: Kuan-yu
authors: KY
authors: Chen
authors: Department of Biotechnology, College of Medicine and Nursing, Hung Kuang University, Taichung, Tainan.
authors: Chao-chung
authors: CC
authors: Chen
authors: Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan.
authors: Yau-lin
authors: YL
authors: Tseng
authors: Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan.
authors: Yi-chien
authors: YC
authors: Chang
authors: Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan. Department of Nutrition, College of Medicine and Nursing, Hung Kuang University, Taichung, Tainan.
authors: Ming-chung
authors: MC
authors: Chang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D011485:Protein Binding; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C485815:CCNDBP1 protein, human; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins