ANGPTL3 is a novel biomarker as it activates ERK/MAPK pathway in oral cancer.
ANGPTL3 is a novel biomarker as it activates ERK/MAPK pathway in oral cancer.
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Angptl3是一种新型的生物标志物，因为它激活了口腔癌中的ERK/MAPK途径。
DOI：
10.1002/cam4.418
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发表时间：
2015-05
期刊：
影响因子：
4
通讯作者：
Uzawa, Katsuhiro
中科院分区：
文献类型：
--
作者：
Koyama, Tomoyoshi;Ogawara, Katsunori;Kasamatsu, Atsushi;Okamoto, Atsushi;Kasama, Hiroki;Minakawa, Yasuyuki;Shimada, Ken;Yokoe, Hidetaka;Shiiba, Masashi;Tanzawa, Hideki;Uzawa, Katsuhiro
关键词：
血管生成素样蛋白3（ANGPTL 3）参与新血管的生长和促分裂原活化蛋白激酶（MAPK）的刺激，在几种类型的人类癌症中异常表达。然而，关于ANGPTL 3在口腔鳞状细胞癌（OSCC）行为中的相关性知之甚少。在这项研究中，我们评估了ANGPTL 3 mRNA和蛋白在OSCC衍生的细胞系（n = 8）和原代OSCC（n = 109），并评估了ANGPTL 3对OSCC的生物学和功能的影响，在体外和体内。与正常对照相比，在细胞系和大多数原发性OSCC（60%）中检测到显著（P < 0.05）ANGPTL 3上调。ANGPTL 3表达水平与肿瘤大小密切相关（P < 0.05）。在T3/T4肿瘤患者中，ANGPTL 3阳性肿瘤的总生存率显著低于ANGPTL 3阴性病例（P < 0.05）。在体外，ANGPTL 3敲减细胞的细胞生长显著（P < 0.05）降低，细胞外调节激酶（ERK）失活，细胞周期停滞在G1期，这是由于细胞周期蛋白依赖性激酶抑制剂（包括p21 Cip 1和p27 Kip 1）的上调。我们还观察到ANGPTL 3敲减细胞异种移植物的生长显著降低（P < 0.05），相对于对照细胞异种移植物，磷酸化ERK水平降低。目前的数据表明，ANGPTL 3可能通过MAPK信号级联在OSCC中发挥作用，使其成为用于OSCC患者的潜在有用的诊断/治疗靶点。
Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth and stimulation of mitogen-activated protein kinase (MAPK), is expressed aberrantly in several types of human cancers. However, little is known about the relevance of ANGPTL3 in the behavior of oral squamous cell carcinoma (OSCC). In this study, we evaluated ANGPTL3 mRNA and protein in OSCC-derived cell lines (n = 8) and primary OSCCs (n = 109) and assessed the effect of ANGPTL3 on the biology and function of OSCCs in vitro and in vivo. Significant (P < 0.05) ANGPTL3 upregulation was detected in the cell lines and most primary OSCCs (60%) compared with the normal counterparts. The ANGPTL3 expression level was correlated closely (P < 0.05) with tumoral size. In patients with T3/T4 tumors, the overall survival rate with an ANGPTL3-positive tumor was significantly (P < 0.05) lower than that of ANGPTL3-negative cases. In vitro, cellular growth in ANGPTL3 knockdown cells significantly (P < 0.05) decreased with inactivated extracellular regulated kinase (ERK) and cell-cycle arrest at the G1 phase resulting from upregulation of the cyclin-dependent kinase inhibitors, including p21Cip1 and p27Kip1. We also observed a marked (P < 0.05) reduction in the growth in ANGPTL3 knockdown-cell xenografts with decreased levels of phosphorylated ERK relative to control-cell xenografts. The current data indicated that ANGPTL3 may play a role in OSCCs via MAPK signaling cascades, making it a potentially useful diagnostic/therapeutic target for use in patients with OSCC.
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