机构:[1]Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.[2]Department of Hematology, The Third Affiliated Hospital, Institute of Hematology Sun Yat-sen University, Guangzhou, China.[3]Department of Medical Oncology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.其他科室肿瘤科中山大学附属第一医院[4]Department of Oncology, The First Hospital Affiliated to Dalian Medical University, Dalian, China.内科科室肿瘤科大连医科大学附属第一医院[5]Department of Hematology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.[6]Department of Thoracic Surgery, The First Hospital Affiliated to Dalian Medical University, Dalian, China.外科科室胸外科大连医科大学附属第一医院[7]Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.其他部门华南肿瘤学国家重点实验室中山大学肿瘤防治中心
Tumor local invasion is the first step of metastasis cascade which remains the key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective invasion in a real time manner. Herein we aim to develop a three-dimensional (3D) microfluidic cell invasion model to determine the dynamic process. In this model, collective invasion of breast cancer cells is induced by the concentration gradient of fetal bovine serum. We find that breast cancer cells adopt a collective movement rather than a random manner when the cells invade into extracellular matrix. The leading cells in the collective movement exhibit an increased expression of an Aurora kinase family protein - AURKA compared with the follower cells. Inhibition of AURKA kinase activity by VX680 or AKI603 significantly reduces the phosphorylation of ERK1/2 (Thr202/Tyr204) and collective cohort formation. Together, our study illustrates that AURKA acts as a potential therapeutic target for suppressing the process of tumor collective invasion. The 3D microfluidic cell invasion model is a reliable, measurable and dynamic platform for exploring potential drugs to inhibit tumor collective invasion.
基金:
National Natural Science Foundation of China [81630005, 81573025, 81602585, 81402445]; Science and Technology Planning Project of Guangzhou [201604020163]; Liaoning NSF [2014029102]; Dalian high-level talent innovation program [2016RD12]
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|3 区综合性期刊
小类|3 区综合性期刊
最新[2023]版:
大类|2 区综合性期刊
小类|2 区综合性期刊
第一作者:
第一作者机构:[1]Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
共同第一作者:
通讯作者:
通讯机构:[1]Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.[2]Department of Hematology, The Third Affiliated Hospital, Institute of Hematology Sun Yat-sen University, Guangzhou, China.[7]Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
推荐引用方式(GB/T 7714):
Jiang-Long Xia,Wen-Jun Fan,Fei-Meng Zheng,et al.Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform[J].SCIENTIFIC REPORTS.2017,7(1):-.doi:10.1038/s41598-017-02623-1.
APA:
Jiang-Long Xia,Wen-Jun Fan,Fei-Meng Zheng,Wen-Wen Zhang,Jia-Jun Xie...&Quentin Liu.(2017).Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform.SCIENTIFIC REPORTS,7,(1)
MLA:
Jiang-Long Xia,et al."Inhibition of AURKA kinase activity suppresses collective invasion in a microfluidic cell culture platform".SCIENTIFIC REPORTS 7..1(2017):-