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Downregulation of p57 kip2 promotes cell invasion via LIMK/cofilin pathway in human nasopharyngeal carcinoma cells
Author(s) -
Chow ShuEr,
Wang JongShyan,
Lin MingRung,
Lee Chien Lin
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23277
Subject(s) - cofilin , cell migration , microbiology and biotechnology , biology , actin cytoskeleton , cell growth , downregulation and upregulation , cell , cell cycle , cancer research , cytoskeleton , biochemistry , gene
The members of Rho family are well known for their regulation of actin cytoskeleton to control cell migration. The Cip/kip members of cyclin‐dependent (CDK) inhibitors have shown to implicate in cell migration and cytoskeletal dynamics. p57 kip2 , a CDK inhibitor, is frequently down‐regulated in several malignancy tumors. However, its biological roles in human nasopharyngeal carcinoma (NPC) cells remained to be investigated. Here, we found p57 kip2 has nuclear and cytoplasm distributions and depletion of endogenous p57 kip2 did not change the cell‐cycle progression. Inhibition of cell proliferation by mitomycin C promoted FBS‐mediated cell migration and accompanied with the downregulation of ΔNp63α and p57 kip2 , but did not change the level of p27 kip1 , another CDK inhibitor. By using siRNA transfection and cell migration/invasion assays, we found that knockdown of p57 kip2 , but not ΔNp63α, involved in promotion of NPC cell migration and invasion via decrease of phospho‐cofilin (p‐cofilin). Treatment with Y‐27632, a specific ROCK inhibitor, we found that dysregulation of ROCK/cofilin pathway decreased p‐cofilin expression and induced cell migration. This change of p‐cofilin induced actin remodeling and pronounced increase of membrane protrusions. Further, silence of p57 kip2 not only decreased the interaction between p57 kip2 and LIMK‐1 assayed by immunoprecipitation but also reduced the level of phospho‐LIMK1/2. Therefore, this study indicated that dysregulation of p57 kip2 promoted cell migration and invasion through modulation of LIMK/cofilin signaling and suggested this induction of inappropriate cell motility might contribute to promoting tumor cell for metastasis. J. Cell. Biochem. 112: 3459–3468, 2011. © 2011 Wiley Periodicals, Inc.