Li Yintao, Bai Menglin, Xu Yali, Zhao Weiwei, Liu Naijia, Yu Jinming
School of Medicine, Shandong University, Jinan, China.
Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
Cell Physiol Biochem. 2018;50(5):2004-2016. doi: 10.1159/000494892. Epub 2018 Nov 7.
BACKGROUND/AIMS: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis.
RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo.
In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS).
Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.
背景/目的：非小细胞肺癌（NSCLC）是癌症死亡的主要原因，肿瘤转移是肺癌相关死亡的主要原因。我们之前的研究发现微管蛋白聚合促进蛋白家族成员3（TPPP3）在NSCLC中作为一种潜在的癌基因发挥作用。关于TPPP3在肿瘤转移中的功能知之甚少。
采用RT-qPCR和免疫组化法检测NSCLC组织中TPPP3的表达。采用CCK8法和Transwell法检测NSCLC细胞的体外增殖和迁移能力，并建立异种移植模型评估体内肿瘤的生长和转移情况。
在本研究中，发现TPPP3的上调与NSCLC转移能力的增加相关。TPPP3的异位表达显著增强了体外细胞增殖并促进了体内肿瘤生长。此外，TPPP3的过表达在体外和体内均显著促进了NSCLC细胞的迁移和侵袭，同时Twist1表达上调。进一步研究表明，STAT3的激活是TPPP3介导的Twist1上调、细胞迁移和侵袭所必需的。在NSCLC组织中发现TPPP3与Twist1表达之间存在强正相关。NSCLC组织中TPPP3或Twist1低表达的患者预后较好，总生存期（OS）和无病生存期（DFS）更长。
总体而言，本研究表明TPPP3通过STAT3/Twist1途径促进NSCLC的转移。
