title: 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.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan; Biochemistry Section, Department of Chemistry, Faculty of Science, Tanta University, Egypt. Electronic address: biomansour@hotmail.com.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Mansour
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Asano
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan.
authors.forename: K A
authors.initials: KA
authors.lastname: Akter
authors.affiliation: Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan.
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan. Electronic address: tsenga@med.nagoya-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D002465:Cell Movement; D022081:Cell Surface Extensions / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D036961:Matrix Attachment Region Binding Proteins; C412722:PALLD protein, human; D010750:Phosphoproteins; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: Colorectal cancer; Invadopodia; Palladin; SATB2