A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells

Yukio Nishimura, Kiyoko Yoshioka, Ora Bernard, Biborka Bereczky, Kazuyuki Itoh

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)627-638
Number of pages12
JournalHistochemistry and Cell Biology
Volume126
Issue number5
DOIs
Publication statusPublished - Nov 1 2006

Fingerprint

Cofilin 1
Lim Kinases
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Breast Neoplasms
Actin Depolymerizing Factors
Endosomes
Endocytosis
Staining and Labeling
Transferrin Receptors
MCF-7 Cells
Vacuoles
Lysosomes
Actin Cytoskeleton
Neoplasms
Phosphotransferases
Texas red
Ligands
Cell Line

All Science Journal Classification (ASJC) codes

  • Histology
  • Molecular Biology
  • Medical Laboratory Technology
  • Cell Biology

Cite this

A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. / Nishimura, Yukio; Yoshioka, Kiyoko; Bernard, Ora; Bereczky, Biborka; Itoh, Kazuyuki.

In: Histochemistry and Cell Biology, Vol. 126, No. 5, 01.11.2006, p. 627-638.

Research output: Contribution to journalArticle

Nishimura, Yukio ; Yoshioka, Kiyoko ; Bernard, Ora ; Bereczky, Biborka ; Itoh, Kazuyuki. / A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. In: Histochemistry and Cell Biology. 2006 ; Vol. 126, No. 5. pp. 627-638.
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