title: Downregulation of p57kip² promotes cell invasion via LIMK/cofilin pathway in human nasopharyngeal carcinoma cells.
abstract: 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.
authors.affiliation: Center for General Studies, Chang Gung University, Taoyuan, Taiwan. chowse@mail.cgu.edu.tw
authors.forename: Shu-Er
authors.initials: SE
authors.lastname: Chow
authors.forename: Jong-Shyan
authors.initials: JS
authors.lastname: Wang
authors.forename: Ming-Rung
authors.initials: MR
authors.lastname: Lin
authors.forename: Chien Lin
authors.initials: CL
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D051338:Cofilin 1 / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D051338:Cofilin 1; D050761:Cyclin-Dependent Kinase Inhibitor p57; D034741:RNA, Small Interfering; D054461:Lim Kinases