title: Cyclin-dependent kinase 5 regulates the proliferation, motility and invasiveness of lung cancer cells through its effects on cytoskeletal remodeling.
abstract: Determining the molecular phenotype is a key to understanding and predicting the metastatic potential and the prognosis for patients with lung cancer. Our previous study demonstrated that increased expression of cyclin‑dependent kinase 5 (CDK5) in patients with non‑small cell lung cancer (NSCLC) is associated with a poorer prognosis. The present study aimed to further investigate the underlying mechanism of CDK5 in vitro and in vivo using the A549 human NSCLC cell line. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was used to quantify the proliferation of the A549 cells; migration assay and invasiveness assays were performed using Transwell chambers and wound healing assays were used to assess cell motility, which was assessed by measuring the movement of cells. Inhibition of CDK5 by roscovitine and small interfering (si)RNA was used to investigate the mechanism of CDK5 in the process of A549 lung cancer cell proliferation, migration and invasion. The results demonstrated that functional inhibition of CDK5 using roscovitine and siRNA markedly suppressed the proliferation of A549 cells and resulted in a reduced tumor mass in vivo. In addition, the hinhibition of CDK5 reduced the migration and invasiveness of the A549 cells in vitro and in vivo. Notably, CDK5 inhibition also impaired tumor cell cytoskeletal remodeling and led to loss of cell polarity, which may partially explain the reduction of A549 cell mobility and invasiveness. The results of the present study revealed that CDK5 may be important in the regulation of migration and invasiveness in NSCLC through its effects on cytoskeletal remodeling.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Run-Xia
authors.initials: RX
authors.lastname: Gu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Xiao-Shu
authors.initials: XS
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Suizhou Central Hospital, Suizhou, Hubei 441300, P.R. China.
authors.forename: Fang-Zheng
authors.initials: FZ
authors.lastname: Zhou
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077546:Roscovitine
chemical_list: D000970:Antineoplastic Agents; D011687:Purines; D034741:RNA, Small Interfering; D000077546:Roscovitine; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human