Abstract
Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate cellular functions other than cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27(kip1) affects microtubule (MT) stability following cell adhesion on extracellular matrix (ECM) constituents. This p27(kip1) activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27(kip1) or downregulation of stathmin expression results in the inhibition of mesenchymal cell motility. Moreover, high stathmin and low cytoplasmic p27(kip1) expression correlate with the metastatic phenotype of human sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor cells based on diverse activities of p27(kip1) in different subcellular compartments.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Adhesion
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism*
-
Cell Line, Tumor
-
Cell Movement*
-
Cells, Cultured
-
Cyclin-Dependent Kinase Inhibitor p27
-
Enzyme Inhibitors / metabolism
-
Extracellular Matrix / metabolism
-
Fibroblasts / cytology
-
Fibroblasts / physiology
-
Fibronectins / metabolism
-
Genes, Tumor Suppressor
-
Humans
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Microtubule Proteins / genetics
-
Microtubule Proteins / metabolism*
-
Microtubules / metabolism
-
Neoplasm Metastasis
-
Phenotype
-
Phosphoproteins / genetics
-
Phosphoproteins / metabolism*
-
Sarcoma / metabolism*
-
Sarcoma / pathology*
-
Stathmin
-
Tubulin / genetics
-
Tubulin / metabolism
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism*
Substances
-
Cdkn1b protein, mouse
-
Cell Cycle Proteins
-
Enzyme Inhibitors
-
Fibronectins
-
Microtubule Proteins
-
Phosphoproteins
-
STMN1 protein, human
-
Stathmin
-
Stmn1 protein, mouse
-
Tubulin
-
Tumor Suppressor Proteins
-
Cyclin-Dependent Kinase Inhibitor p27