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

2015; Wiley; Volume: 4; Issue: 5 Linguagem: Inglês

10.1002/cam4.418

2045-7634

Tomoyoshi Koyama, Katsunori Ogawara, Atsushi Kasamatsu, Atsushi Okamoto, Hiroki Kasama, Yasuyuki Minakawa, Ken Shimada, Hidetaka Yokoe, Masashi Shiiba, Hideki Tanzawa, Katsuhiro Uzawa,

Kruppel-like factors research

Abstract Angiopoietin‐like 3 ( ANGPTL 3), 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 ANGPTL 3 in the behavior of oral squamous cell carcinoma ( OSCC ). In this study, we evaluated ANGPTL 3 mRNA and protein in OSCC ‐derived cell lines ( n = 8) and primary OSCC s ( n = 109) and assessed the effect of ANGPTL 3 on the biology and function of OSCC s in vitro and in vivo. Significant ( P < 0.05) ANGPTL 3 upregulation was detected in the cell lines and most primary OSCC s (60%) compared with the normal counterparts. The ANGPTL 3 expression level was correlated closely ( P < 0.05) with tumoral size. In patients with T3/T4 tumors, the overall survival rate with an ANGPTL 3‐positive tumor was significantly ( P < 0.05) lower than that of ANGPTL 3‐negative cases. In vitro, cellular growth in ANGPTL 3 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 ANGPTL 3 knockdown‐cell xenografts with decreased levels of phosphorylated ERK relative to control‐cell xenografts. The current data indicated that ANGPTL 3 may play a role in OSCC s via MAPK signaling cascades, making it a potentially useful diagnostic/therapeutic target for use in patients with OSCC .