IGFBP‐6 plays a role as an oncosuppressor gene in NPC pathogenesis through regulating EGR‐1 expression

Kuo, Ya‐Huei; Tang, Yueh‐Bih; Lu, Tung-Ying; Wu, Han-Chung; Lin, Chien-Ching

doi:10.1002/path.2735

Cited by 35 publications

(29 citation statements)

References 38 publications

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“…Fung, et al reported that IGF receptor II was overexpressed in malignant nasopharyngeal epithelial cells [29]. Only one in vitro study proposed that IGFBP6 is a tumor suppressor in NPC [27]. …”

Section: Discussionmentioning

confidence: 99%

“…Increased IGFBP6 expression correlated with increasing degrees of brain tissue invasion by meningioma cells [25, 26]. Only one report proposed that IGFBP6 acts as a tumor suppressor gene in NPC [27], and the biological functions of IGFBP6 in NPC progression remain unclear. In the current study, we explored the effects of IGFBP6 on NPC progression and evaluated IGFBP6 as a potential independent NPC prognostic biomarker.…”

Section: Introductionmentioning

confidence: 99%

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IGFBP6 is a novel nasopharyngeal carcinoma prognostic biomarker

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IGFBP6 is a novel nasopharyngeal carcinoma prognostic biomarker

et al. 2016

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“…Low serum IGFBP-3 is associated with greater risk of aggressive and metastatic PCa (Chan et al 2002;Mehta et al 2011). Interestingly, IGFBP-6 inhibits PCa cell proliferation (Koike et al 2005), and acts as a tumor suppressor gene during nasopharyngeal carcinoma pathogenesis (Kuo et al 2010), implying that it may be a promising biomarker for PCa like IGFBP-3.…”

Section: Introductionmentioning

confidence: 99%

CC Chemokine Ligand 18 and IGF-Binding Protein 6 as Potential Serum Biomarkers for Prostate Cancer

Zhang

Sun

et al. 2014

Tohoku J. Exp. Med.

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Prostate cancer (PCa) is the second leading cause of cancer-related death in men globally. However, there are few sensitive biomarkers for PCa, especially those which can distinguish PCa and benign prostate hyperplasia (BPH). Antibody microarrays allow for high-throughput and high-sensitivity detection of multiple proteins simultaneously, providing a powerful tool for biomarker screening. Here, we selected 46 patients with PCa and 42 controls with BPH, and compared the serum levels of different cytokines in PCa and BPH patients using antibody microarrays. The results indicated that serum levels of macrophage colonystimulating factor (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa patients than those in BPH patients, while serum levels of insulin-like growth factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly lower. M-CSF and Fas/TNFRSF6 have been reported to be associated with PCa pathogenesis, and thus were used as positive controls in the present study. CCL-18 is a chemokine primarily involved in recruitment of the adaptive immune system, while IGFBP-6 has been reported to inhibit proliferation of PCa cells. Serum levels of these four cytokines could distinguish PCa from BPH with high sensitivity and high specificity. Furthermore, the area under the ROC curve (AUC) was above 0.925 and 0.835 for CCL-18 and IGFBP-6, respectively, implying their high diagnostic value. In conclusion, we have identified CCL-18 and IGFBP-6 as new potential serum biomarkers for PCa.Keywords: benign prostate hyperplasia; biomarker; CC chemokine ligand 18; insulin-like growth factor-binding protein 6; prostate cancer Tohoku J.

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“…IGFBP-6 can completely inhibit IGF-II-induced proliferation and adhesion effects in colon cancer cells (Leng et al, 2001). Similarly, over-expression of IGFBP-6 significantly suppresses the proliferation, invasion and metastatic activity of nasopharyngeal carcinoma cells and increases their apoptosis by regulating the expression of EGR-1 (Kuo et al, 2010). In EC tissues, the mean IGFBP-6 mRNA level is similar to that in cycling endometrium during the peri-ovulatory period (Rutanen et al, 1994).…”

Section: Discussionmentioning

confidence: 88%