Effects of stable knockdown of Aurora kinase A on proliferation, migration, chromosomal instability, and expression of focal adhesion kinase and matrix metalloproteinase-2 in HEp-2 cells.

Abstract

Overexpression of Aurora kinase A (AURKA) is frequently observed in various cancers, including laryngeal squamous cell carcinoma (LSCC). We investigated the effects of knockdown of AURKA on laryngeal cancer HEp-2 cells both in vitro and in vivo. A plasmid containing short hairpin (sh)RNA against AURKA was constructed and transfected into HEp-2. Measurements included the CCK-8 assay for viability and proliferation, flow cytometry for apoptosis and effects on the mitotic checkpoint, a trans-well assay for migration, immunofluorescence for assessment of genomic instability, and western blotting for protein expression. AURKA knockdown inhibited proliferation, migration, and colony formation in vitro and tumorigenicity in vivo. The knockdown induced the accumulation of cells in G2-M phase and eventual apoptosis. Knockdown of AURKA caused delayed entry into mitosis after treatment with nocodazole, reduced chromosomal instability, and decreased expression of focal adhesion kinase (FAK), phosphorylated FAK, and matrix metalloproteinase-2 (MMP-2), key regulators in cell adhesion and invasion. Knockdown of AURKA inhibits the growth and invasiveness of this LSCC cell line both in vitro and in vivo. These effects may partially result from the reduced expression of FAK and MMP-2. Knockdown of AURKA expression may represent a promising therapeutic strategy for the treatment of LSCC.

• Authors: Hao Zhang, Xuehua Chen, Bingya Liu, Liang Zhou
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 357 Issue 1-2 Pg. 95-106 (Nov 2011) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 21590355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Focal Adhesion Protein-Tyrosine Kinases
• AURKA protein, human
• Aurka protein, mouse
• Aurora Kinase A
• Aurora Kinases
• Protein Serine-Threonine Kinases
• Matrix Metalloproteinase 2

Topics

• Animals
• Aurora Kinase A
• Aurora Kinases
• Carcinogenicity Tests
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Chromosomal Instability (genetics)
• Focal Adhesion Protein-Tyrosine Kinases (genetics, metabolism)
• Gene Knockdown Techniques
• Humans
• Laryngeal Neoplasms (metabolism)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Mice
• Mice, Nude
• Protein Serine-Threonine Kinases (genetics, metabolism)
• RNA Interference