IGFBP6 is a novel nasopharyngeal carcinoma prognostic biomarker.
Insulin-like growth factor binding proteins (IGFBPs) play critical roles in carcinogenesis. This study assessed the impact of IGFBP6 on the progression of nasopharyngeal carcinoma (NPC). Using immunohistochemical analysis, we found that IGFBP6 was differentially expressed in primary malignant NPC tissues. Clinical samples were divided into two groups: IGFBP6(+) and IGFBP6(-). Five years of follow-up revealed that overall survival and distant metastasis-free survival rates were significantly higher in the IGFBP6(+) than IGFBP6(-) group. We also used real-time PCR, ELISA and western blot assays to measure IGFBP6 levels in five NPC cell lines (CNE1, CNE2, HONE1, HK1 and SUNE1). All the cell lines expressed IGFBP6, but at different levels, reflecting disease heterogeneity. In addition, exogenous expression of IGFBP6 inhibited CNE2 cell proliferation and invasion in vitro. IGFBP6 knockdown activated the GSK3β/β-catenin/cyclin D1 pathway and enhanced CNE2 tumor cell growth and metastasis in a mouse model. These results suggest that IGFBP6 may be an independent prognostic biomarker for NPC.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Qiuyan
Q
Chen
Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China.
Siyuan
S
Qin
Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China.
Yang
Y
Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Minghuang
M
Hong
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Chao-Nan
CN
Qian
Department of Urology and Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Evan T
ET
Keller
Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jian
J
Zhang
Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China.|Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Yi
Y
Lu
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D000067492:RNAi Therapeutics; D015398:Signal Transduction / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D014408:Biomarkers, Tumor; D018976:Insulin-Like Growth Factor Binding Protein 6
GSK3β; IGFBP6; cyclin D1; nasopharyngeal carcinoma; β-catenin