ANGPTL3 is a novel biomarker as it activates ERK/MAPK pathway in oral cancer

Cancer Medicine

Tomoyoshi Koyama¹  Katsunori Ogawara²  Atsushi Kasamatsu²  Atsushi Okamoto¹  Hiroki Kasama¹  Yasuyuki Minakawa²  Ken Shimada²  Hidetaka Yokoe⁴  Masashi Shiiba³  Hideki Tanzawa¹ 

[1] Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan;Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan;Department of Clinical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan;Department of Oral and Maxillofacial Surgery Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan

关键词: Angiopoietin‐like 3;    extracellular signal‐regulated MAP Kinases;    head and neck;    squamous cell carcinoma;    survival;   

DOI  :  10.1002/cam4.418

来源: Wiley

【 摘 要 】

Abstract

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 p21^Cip1 and p27^Kip1. 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.

【 授权许可】

CC BY   
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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