Mansour Mohammed A, Asano Eri, Hyodo Toshinori, Akter K A, Takahashi Masahide, Hamaguchi Michinari, Senga Takeshi
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.
Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550 Japan.
Exp Cell Res. 2015 Mar 1;332(1):78-88. doi: 10.1016/j.yexcr.2014.12.003. Epub 2014 Dec 15.
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.
侵袭性伪足是基于肌动蛋白的特化质膜微结构域，它将黏附特性与基质降解活性结合在一起。骨骼、免疫和血管系统的正常功能依赖于这些细胞器，并且它们在癌细胞中的作用与肿瘤转移相关。阐明驱动侵袭性伪足形成的机制是理解其作用并最终控制其功能的前提条件。据报道，富含AT序列结合蛋白2（SATB2）可抑制肿瘤细胞迁移和转移。然而，SATB2的作用机制尚不清楚。在此，我们表明SATB2抑制HCT116细胞中侵袭性伪足的形成，并且SATB2的外源性表达会抑制分子支架蛋白帕拉丁。为证实这种关联，我们使用敲低策略阐明了帕拉丁在HCT116中的功能。敲低帕拉丁可减少细胞迁移和侵袭，并抑制侵袭性伪足的形成。这一表型通过拯救实验得到证实。然后我们证明，在表达SATB2的细胞中表达帕拉丁可恢复侵袭和侵袭性伪足的形成。我们的结果表明，SATB2的作用是通过抑制帕拉丁介导的，并且SATB2/帕拉丁途径与结肠癌细胞中侵袭性伪足的形成相关。
