| RRC ID |
36776
|
| 著者 |
Koyama T, Ogawara K, Kasamatsu A, Okamoto A, Kasama H, Minakawa Y, Shimada K, Yokoe H, Shiiba M, Tanzawa H, Uzawa K.
|
| タイトル |
ANGPTL3 is a novel biomarker as it activates ERK/MAPK pathway in oral cancer.
|
| ジャーナル |
Cancer Med
|
| 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.
|
| 巻・号 |
4(5)
|
| ページ |
759-69
|
| 公開日 |
2015-5-1
|
| DOI |
10.1002/cam4.418
|
| PMID |
25644496
|
| PMC |
PMC4430268
|
| MeSH |
Adult
Aged
Aged, 80 and over
Angiopoietin-Like Protein 3
Angiopoietin-like Proteins
Angiopoietins / genetics
Angiopoietins / metabolism*
Animals
Biomarkers
Carcinoma, Squamous Cell / metabolism
Cell Line, Tumor
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Heterografts
Humans
MAP Kinase Signaling System*
Male
Middle Aged
Mouth Neoplasms / genetics
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
ROC Curve
Tumor Burden
Up-Regulation
|
| IF |
3.491
|
| 引用数 |
35
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HO-1-u-1(RCB2102)
HSC-2(RCB1945)
HSC-3(RCB1975)
HSC-4(RCB1902)
Sa3(RCB0980)
Ca9-22(RCB1976) |
