BACKGROUND There are seven insulin-like growth factor binding proteins (IGFBPs) that bind insulin-like growth factors (IGFs). IGFBP like protein1 (IGFBPL1) is a new member of this family. The function and mechanism of IGFBPL1 in esophageal cancer remains to be elucidated. METHODS Eight esophageal cancer cell lines, 114 cases of esophageal dysplasia, and 501 cases of primary esophageal cancer samples were examined in this study. Methylation-specific polymerase chain reaction (MSP), immunohistochemistry, Western blot, flow cytometry, RNA interference assay, and xenograft mouse models were employed. RESULTS The expression of IGFBPL1was lost and complete methylation was found in KYSE150 and KYSE410 cells. Reduced expression and partial methylation of IGFBPL1 was found in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells. High expression and unmethylation was detected in KYSE510 cells. Restoration of IGFBPL1 expression was found in KYSE150 and KYSE410 cells and the expression of IGFBPL1 was increased in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells, after 5-AZA-2'-deoxycytidine treatment. IGFBPL1 was methylated in 47.3% (53/114) of esophageal dysplasia and 49.1% (246/501) of human primary esophageal squamous cell carcinoma (ESCC). Methylation of IGFBPL1 was significantly associated with TNM stage (p = 0.012), and tumor size (p = 0.009). IGFBPL1 inhibited esophageal cancer cell clonal formation and proliferation and induced cell apoptosis and G1/S phase arrest. Further study found that IGFBPL1 is involved in PI3K-AKT signaling and IGFBPL1 suppressed human ESCC xenografts growth in mice. CONCLUSION IGFBPL1 suppresses esophageal cancer cell growth by inhibiting PI3K-AKT signaling in vitro and in vivo. IGFBPL1 is a novel tumor suppressor in human esophageal cancer.

中文翻译：

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IGFBPL1的表观遗传沉默通过激活PI3K-AKT信号传导促进食道癌的生长。

背景技术有七个胰岛素样生长因子结合蛋白（IGFBP）结合胰岛素样生长因子（IGF）。IGFBP像蛋白1（IGFBPL1）是该家族的新成员。IGFBPL1在食管癌中的功能和机制尚待阐明。方法研究八种食管癌细胞系，114例食管异型增生和501例原发性食管癌标本。使用甲基化特异性聚合酶链反应（MSP），免疫组织化学，蛋白质印迹，流式细胞仪，RNA干扰测定和异种移植小鼠模型。结果IGFBPL1的表达丢失，在KYSE150和KYSE410细胞中发现了完全甲基化。在Bic1，KYSE140，KYSE450，KYSE520和COLO680N细胞中发现IGFBPL1的表达降低和部分甲基化。在KYSE510细胞中检测到高表达和未甲基化。5-AZA-2'-脱氧胞苷处理后，在KYSE150和KYSE410细胞中发现IGFBPL1表达恢复，在Bic1，KYSE140，KYSE450，KYSE520和COLO680N细胞中IGFBPL1表达增加。IGFBPL1在47.3％（53/114）的食管发育不良和49.1％（246/501）的人原发性食管鳞状细胞癌（ESCC）中被甲基化。IGFBPL1的甲基化与TNM分期（p = 0.012）和肿瘤大小（p = 0.009）显着相关。IGFBPL1抑制食管癌细胞克隆的形成和增殖，并诱导细胞凋亡和G1 / S期阻滞。进一步的研究发现，IGFBPL1参与了PI3K-AKT信号传导，并且IGFBPL1抑制了人类ESCC异种移植小鼠的生长。结论IGFBPL1通过在体内外抑制PI3K-AKT信号传导来抑制食管癌细胞的生长。IGFBPL1是人类食道癌中的新型肿瘤抑制剂。