title: Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition.
abstract: Integrin-linked kinase (ILK) is a multifunctional serine/threonine kinase. Accumulating evidences suggest that ILK are involved in cell-matrix interactions, cell proliferation, invasion, migration, angiogenesis and Epithelial-mesenchymal transition (EMT). However, the underlying mechanisms remain largely unknown. EMT has been postulated as a prerequisite for metastasis. The reports have demonstrated that EMT was implicated in metastasis of oral squamous cell carcinomas. Therefore, here we further postulate that ILK might participate in EMT of tongue cancer. We showed that ILK siRNA inhibited EMT with low N-cadherin, Vimentin, Snail, Slug and Twist as well as high E-cadherin expression in vivo and in vitro. We found that knockdown of ILK inhibited cell proliferation, migration and invasion as well as changed cell morphology. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3β as well as reduced expression of MMP2 and MMP9. Furthermore, we found that the tongue tumor with high metastasis capability showed higher ILK, Vimentin, Snail, Slug and Twist as well as lower E-cadherin expression in clinical specimens. Finally, ILK siRNA led to the suppression for tumorigenesis and metastasis in vivo. Our findings suggest that ILK could be a novel diagnostic and therapeutic target for tongue cancer.
authors.affiliation: College of Laboratory Medicine, Chongqing Medical University, Chongqing, China; Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xing
authors.affiliation: The Affiliated Hospital of Stomatology, Chongqing Medical University, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: College of Laboratory Medicine, Chongqing Medical University, Chongqing, China; Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, China.
authors.forename: Shixiong
authors.initials: S
authors.lastname: Deng
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China; Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors.forename: Luyu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China; Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China. Electronic address: chjunxia@126.com.
authors.forename: Junxia
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK
keywords: Epithelial–mesenchymal transition (EMT); Integrin-linked kinase; Metastasis; Tongue cancer cells