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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. Highlights: • ILKmore » siRNA influences cell morphology, cell cycle, migration and invasion. • ILK siRNA affects the expression of proteins associated with EMT. • ILK expression is related to EMT in clinical human tongue tumors. • ILK siRNA inhibits metastasis of the tongue cancer cells through suppressing EMT.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [4];  [2];  [4];  [4];  [2]
  1. College of Laboratory Medicine, Chongqing Medical University, Chongqing (China)
  2. (China)
  3. The Affiliated Hospital of Stomatology, Chongqing Medical University (China)
  4. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing (China)
Publication Date:
OSTI Identifier:
22271327
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 319; Journal Issue: 13; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; CARCINOMAS; CELL CYCLE; CELL PROLIFERATION; IN VITRO; IN VIVO; METASTASES; RNA; SERINE; THREONINE; TONGUE

Citation Formats

Xing, Yu, Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, Qi, Jin, Deng, Shixiong, Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, Wang, Cheng, Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, Zhang, Luyu, Chen, Junxia, E-mail: chjunxia@126.com, and Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing. Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition. United States: N. p., 2013. Web. doi:10.1016/J.YEXCR.2013.05.014.
Xing, Yu, Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, Qi, Jin, Deng, Shixiong, Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, Wang, Cheng, Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, Zhang, Luyu, Chen, Junxia, E-mail: chjunxia@126.com, & Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing. Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition. United States. doi:10.1016/J.YEXCR.2013.05.014.
Xing, Yu, Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, Qi, Jin, Deng, Shixiong, Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing, Wang, Cheng, Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, Zhang, Luyu, Chen, Junxia, E-mail: chjunxia@126.com, and Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing. Thu . "Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition". United States. doi:10.1016/J.YEXCR.2013.05.014.
@article{osti_22271327,
title = {Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition},
author = {Xing, Yu and Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing and Qi, Jin and Deng, Shixiong and Laboratory of Forensic Medicine and Biomedical Information, Chongqing Medical University, Chongqing and Wang, Cheng and Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing and Zhang, Luyu and Chen, Junxia, E-mail: chjunxia@126.com and Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing},
abstractNote = {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. Highlights: • ILK siRNA influences cell morphology, cell cycle, migration and invasion. • ILK siRNA affects the expression of proteins associated with EMT. • ILK expression is related to EMT in clinical human tongue tumors. • ILK siRNA inhibits metastasis of the tongue cancer cells through suppressing EMT.},
doi = {10.1016/J.YEXCR.2013.05.014},
journal = {Experimental Cell Research},
number = 13,
volume = 319,
place = {United States},
year = {Thu Aug 01 00:00:00 EDT 2013},
month = {Thu Aug 01 00:00:00 EDT 2013}
}