CRN2 enhances the invasiveness of glioblastoma cells.

Abstract

BACKGROUND:

Movement of tumor cells involves dynamic remodeling of the actin cytoskeleton, which is regulated by actin binding proteins, such as CRN2 (synonyms: coronin 1C, coronin 3). In vitro, CRN2 participates in secretion, matrix degradation, protrusion formation, and cell migration. Furthermore, expression of CRN2 correlates with the malignant phenotype of human diffuse gliomas. CRN2's effects on actin polymerization and F-actin bundling are abolished by protein kinase 2 (CK2) dependent phosphorylation at serine 463.

METHODS:

We generated human U373 glioblastoma cell lines with knock-down of CRN2 or over-expression of CRN2 variants and studied their behavior in vitro and ex vivo in organotypic brain slice cultures.

RESULTS:

CRN2 over-expression and expression of the S463A phospho-resistant CRN2 variant increase proliferation, matrix degradation, and invasion but decrease adhesion and formation of invadopodia-like extensions in vitro. Knock-down of CRN2 and expression of S463D phospho-mimetic CRN2 generally have opposite effects. Analysis of invadopodia-like cell extensions shows a diffuse relocalization of F-actin in CRN2 knockdown cells, whereas expression of S463A and S463D mutant CRN2 causes enrichments of F-actin structures at the center and rime zone, respectively. Fluorescence recovery after photobleaching studies of CRN2 and F-actin in lamellipodia show that both CRN2 variants decrease the turnover of actin filaments. Glioblastoma cells over-expressing wild-type or S463A CRN2, which were transplanted onto brain slices, characteristically developed into tumors with an invasive phenotype.

CONCLUSIONS:

Overall, our data indicate that CRN2 participates in cancer progression via modulation of the actin cytoskeleton.

• Authors: Anja Ziemann, Simon Hess, Ridhirama Bhuwania, Stefan Linder, Peter Kloppenburg, Angelika A Noegel, Christoph S Clemen
• Journal: Neuro-oncology (Neuro Oncol) Vol. 15 Issue 5 Pg. 548-61 (May 2013) ISSN: 1523-5866 [Electronic] England
• PMID: 23410663 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Microfilament Proteins
• RNA, Small Interfering
• coronin proteins

Topics

• Actin Cytoskeleton (metabolism)
• Actins (metabolism)
• Animals
• Apoptosis
• Blotting, Western
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Cell Surface Extensions
• Glioblastoma (metabolism, pathology)
• Humans
• Mice
• Mice, Inbred C57BL
• Microfilament Proteins (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Invasiveness
• Organ Culture Techniques
• Phosphorylation
• Pseudopodia (metabolism, pathology)
• RNA, Small Interfering (genetics)
• Tumor Cells, Cultured