title: Effects of lentivirus-mediated shRNA targeting integrin-linked kinase on oral squamous cell carcinoma in vitro and in vivo.
abstract: Integrin-linked kinase (ILK), a highly conserved intracellular protein of serine/threonine protein kinase activities, which is associated with the integrin and growth factor receptor signaling pathway, is involved in the regulation of cell proliferation, apoptosis, differentiation, migration and epithelial-mesenchymal transition (EMT). Findings of a previous study showed that ILK overexpression was strongly correlated with a more aggressive tumor phenotype, recurrence and poor survival for oral squamous cell carcinoma (OSCC) patients, as well as some EMT markers. In order to investigate the underlying mechanisms involved, a lentivirus-mediated short hairpin RNA (shRNA) was employed to downregulate ILK. The results showed that the knockdown of ILK inhibited cell growth, adhesion and invasion ability in vitro, and OSCC cells deficient of ILK were blocked in the S phase and underwent apoptosis. Additionally, ILK shRNA inhibited EMT by impairing the expression of Snail, Slug and Twist2 and enhacning E-cadherin expression. ILK shRNA suppressed the phosphorylation of downstream signaling targets Akt and GSk-3β. In addition, the knockdown of ILK inhibited tumor growth, invasion and metastasis of xenograft tumors in vivo. These results suggested that ILK is a promising therapeutic target for the treatment of OSCC.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Que
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Head and Neck Carcinoma, West China College of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Xiu-Fa
authors.initials: XF
authors.lastname: Tang
authors.affiliation: Department of Head and Neck Carcinoma, West China College of Stomatology, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK