A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells
- Author(s)
- Nishimura, Y; Yoshioka, K; Bernard, O; Bereczky, B; Itoh, K;
- Details
- Publication Year 2006-11,Volume 126,Issue #5,Page 627-638
- Journal Title
- HISTOCHEMISTRY AND CELL BIOLOGY
- Publication Type
- Journal Article
- Abstract
- We have previously shown that overexpression of LIM kinase1 (LIMK1) resulted in a marked retardation of the internalization of the receptor-mediated endocytic tracer, Texas red-labeled epidermal growth factor (EGF) in low-invasive human breast cancer cell MCF-7. We thereby postulate that LIMK1 signaling plays an important role in the regulation of ligand-induced endocytosis of EGF receptor (EGFR) in tumor cells by reorganizing and influencing actin-filament dynamics. In the present study, we further assessed the effect of wild-type LIMK1, a kinase-deficient dominant negative mutant of LIMK1 (DN-LIMK1) and an active, unphosphorylatable cofilin mutant (S3A cofilin) on internalization of EGF-EGFR in MDA-MB-231, a highly invasive human breast cancer cell line. We demonstrate here that a marked delay in the receptor-mediated internalization of Texas red-labeled EGF was observed in the wild-type LIMK1 transfectants, and that most of the internalized EGF staining were accumulated within transferrin receptor-positive early endosomes even after 30 min internalization. In contrast, the expression of dominant-negative LIMK1 mutant rescued the efficient endocytosis of Texas red-EGF, and large amounts of Texas red-EGF staining already reached LIMPII-positive late endosomes/lysosomal vacuoles after 15 min internalization. We further analyzed the effect of S3A cofilin mutant on EGFR trafficking, and found an efficient delivery of Texas red-EGF into late endosomes/lysosomes at 15-30 min after internalization. Taken together, our novel findings presented in this paper implicate that LIMK1 signaling indeed plays a pivotal role in the regulation of EGFR trafficking through the endocytic pathway in invasive tumor cells.
- Publisher
- SPRINGER
- Keywords
- RHO-ASSOCIATED KINASE; BINDING PROTEIN RHO; TUMOR-CELLS; MEMBRANE-PROTEIN; FOCAL ADHESIONS; ACTIN DYNAMICS; PHOSPHORYLATION; INVASION; ACTIVATION; LYSOSOMES
- Publisher's Version
- https://doi.org/10.1007/s00418-006-0198-x
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-11-01 12:00:00