Lin Lan-Lan, Yang Fan, Zhang Dong-Huan, Hu Cong, Yang Sheng, Chen Xiang-Qi
Department of Respiratory Medicine, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China.
Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China.
Cancer Cell Int. 2021 Jun 26;21(1):320. doi: 10.1186/s12935-021-02022-7.
Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial-mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process.
Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot.
ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells.
ARHGAP10 inhibits the epithelial-mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.
Rho GTP酶激活蛋白10(ARHGAP10)被认为是多种细胞过程中的关键要素,包括细胞迁移、黏附以及肌动蛋白细胞骨架的动态重组。然而,ARHGAP10表达与肺癌细胞上皮-间质转化(EMT)之间的相关性尚不清楚,有待阐明。在此,我们研究了ARHGAP10特性与非小细胞肺癌(NSCLC)病理过程之间的关系。
采用免疫组织化学法评估ARHGAP10在NSCLC组织中的表达。运用CCK-8法、Transwell法、划痕试验评估细胞增殖、侵袭和迁移能力。通过免疫荧光和蛋白质印迹检测EMT生物标志物以及PI3K/Akt/GSK3β信号通路中相关活性分子的表达水平。
与个体正常组织相比,检测发现ARHGAP10在NSCLC组织中表达较低。此外,ARHGAP10过表达抑制了A549和NCI-H1299细胞的迁移和侵袭能力。另外,ARHGAP10通过PI3K/Akt/GSK3β途径直接介导EMT过程。同时,胰岛素样生长因子-1(IGF-1)信号通路的激活逆转了ARHGAP10过表达对NSCLC细胞中EMT的调控。
ARHGAP10通过PI3K/Akt/GSK3β信号通路抑制NSCLC中的上皮-间质转化,这表明相较于传统阿片类药物,ARHGAP10激动剂可能是NSCLC患者的一种可选治疗方法。