Special AT-rich sequence-binding protein 2 suppresses invadopodia formation in HCT116 cells via palladin inhibition.

Abstract

Invadopodia are specialized actin-based microdomains of the plasma membrane that combine adhesive properties with matrix degrading activities. Proper functioning of the bone, immune, and vascular systems depend on these organelles, and their relevance in cancer cells is linked to tumor metastasis. The elucidation of the mechanisms driving invadopodia formation is a prerequisite to understanding their role and ultimately to controlling their functions. Special AT-rich sequence-binding protein 2 (SATB2) was reported to suppress tumor cell migration and metastasis. However, the mechanism of action of SATB2 is unknown. Here, we show that SATB2 inhibits invadopodia formation in HCT116 cells and that the molecular scaffold palladin is inhibited by exogenous expression of SATB2. To confirm this association, we elucidated the function of palladin in HCT116 using a knock down strategy. Palladin knock down reduced cell migration and invasion and inhibited invadopodia formation. This phenotype was confirmed by a rescue experiment. We then demonstrated that palladin expression in SATB2-expressing cells restored invasion and invadopodia formation. Our results showed that SATB2 action is mediated by palladin inhibition and the SATB2/palladin pathway is associated with invadopodia formation in colorectal cancer cells.

• Authors: Mohammed A Mansour, Eri Asano, Toshinori Hyodo, K A Akter, Masahide Takahashi, Michinari Hamaguchi, Takeshi Senga
• Journal: Experimental cell research (Exp Cell Res) Vol. 332 Issue 1 Pg. 78-88 (Mar 01 2015) ISSN: 1090-2422 [Electronic] United States
• PMID: 25523619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Cytoskeletal Proteins
• Matrix Attachment Region Binding Proteins
• PALLD protein, human
• Phosphoproteins
• SATB2 protein, human
• Transcription Factors

Topics

• Cell Movement
• Cell Surface Extensions (physiology)
• Cytoskeletal Proteins (metabolism)
• HCT116 Cells
• Humans
• Matrix Attachment Region Binding Proteins (physiology)
• Phosphoproteins (metabolism)
• Protein Transport
• Transcription Factors (physiology)