SPARC promotes the proliferation and metastasis of oral squamous cell carcinoma by PI3K/AKT/PDGFB/PDGFR axis
SPARC promotes the proliferation and metastasis of oral squamous cell carcinoma by PI3K/AKT/PDGFB/PDGFR axis
复制标题
SPARC通过PI3K/AKT/PDGFB/PDGFR轴促进口腔鳞癌的增殖和转移
DOI：
10.1002/jcp.28205
复制
发表时间：
2019-09-01
影响因子：
5.6
通讯作者：
Hu, Qingang
中科院分区：
文献类型：
--
作者：
Jing, Yue;Jin, Yue;Hu, Qingang
口腔鳞状细胞癌（Oral squamous cell carcinoma，OSCC）是一种世界范围内高致死率的恶性肿瘤，其5年生存率近60%，预后差。在这里，我们介绍了一种新的分泌性和酸性糖蛋白，富含半胱氨酸（分泌蛋白酸性和富含半胱氨酸，ESTA），这是与最坏的模式的侵袭（WPOI）和预后的口腔鳞癌。采用定量聚合酶链反应和免疫组织化学方法检测口腔鳞癌组织和正常组织中的p53蛋白表达水平。通过细胞计数试剂盒-8、集落形成试验和Edu试验，检测了顺铂对细胞增殖的影响。通过伤口愈合实验和transwell迁移实验检测顺铂对口腔鳞癌细胞转移的影响。其次，分析了STRING所共有的生物学特性。此外，通过蛋白质印迹分析证实了潜在的机制。结果显示，OSCC组织中的表达高于非肿瘤组织。高表达与肿瘤分化差、WPOI模式差和总生存期明显缩短相关。敲低表达抑制OSCC细胞的生长、迁移和侵袭。此外，生物信息学分析发现，PDGFB与血小板衍生生长因子B（PDGFB）和PI 3 K/AKT信号通路存在共表达网络，错误发现率最低。此外，PDGFb、PDGFR、p-PDGFR和PI 3 K/AKT信号通路的表达也可能通过调节PDGFb、PDGFR、p-PDGFR的表达而促进OSCC细胞的转移。在口腔鳞癌中，高表达的WPOI与低分化程度呈正相关。OSCC可激活PI 3 K/AKT/PDGFB/PDGFR轴以促进OSCC细胞系的增殖和转移。因此，OSCC可能是一个潜在的治疗靶点。
Oral squamous cell carcinoma (OSCC) is a highly lethal cancer in the world, and the prognosis of OSCC is poor with a 60% 5-year survival rate in recent decades. Here, we introduced a novel secretory and acid glycoprotein with cysteine rich (secreted protein acidic and rich in cysteine, SPARC), which is correlated with the worst pattern of invasion (WPOI) and prognosis of OSCC. SPARC expression levels were measured in OSCC tissues and normal tissues using quantitative polymerase chain reaction and immunohistochemistry. The influence of SPARC on cell proliferation was examined by cell counting kit-8, colony formation, and Edu tests. Then, the effect of SPARC on the metastasis of OSCC cells was detected by wound healing and transwell migration assays. Next, the biologic characteristics of SPARC shared by STRING were analyzed. Furthermore, the underlying mechanisms were confirmed by western blot analysis. SPARC revealed higher expression in OSCC tissues than nontumor tissues. Higher SPARC expression was correlated with poorer tumor differentiation, poorer WPOI pattern, and significantly and shorter overall survival. Knockdown SPARC significantly restrained OSCC cell growth, migration, and invasion. In addition, bioinformatics analysis found SPARC had a coexpression network with the platelet-derived growth factor-B (PDGFB) and PI3K/AKT signaling pathways with minimal false discovery rate. Furthermore, SPARC promotes OSCC cells metastasis by regulating the expressions of PDGFB, PDGFR, p-PDGFR , and the PI3K/AKT pathway. Higher SPARC expression was positively correlated with poor WPOI and differentiation in OSCC. SPARC activates the PI3K/AKT/PDGFB/PDGFR axis to promote proliferation and metastasis by OSCC cell lines. Therefore, SPARC may be a potential therapeutic target for patients with OSCC.