Abstract：
Compiling evidence has indicated that S100A11 expression at high levels is closely associated with various cancer species. Consistent with the results reported elsewhere, we have also revealed that S100A11 is highly expressed in squamous cell carcinoma, mesothelioma, and pancreatic cancers and plays a crucial role in cancer progression when secreted into extracellular fluid. Those studies are all focused on the extracellular role of S100A11. However, most of S100A11 is still present within cancer cells, although the intracellular role of S100A11 in cancer cells has not been fully elucidated. Thus, we aimed to investigate S100A11 functions within cancer cells, primarily focusing on colorectal cancer cells, whose S100A11 is abundantly present in cells and still poorly studied cancer for the protein. Our efforts revealed that overexpression of S100A11 promotes proliferation and migration, and downregulation inversely dampens those cancer behaviors. To clarify how intracellular S100A11 aids cancer cell activation, we tried to identify S100A11 binding proteins, resulting in novel binding partners in the inner membrane, many of which are desmosome proteins. Our molecular approach defined that S100A11 regulates the expression level of DSG1, a component protein of desmosome, by which S100A11 activates the TCF pathway via promoting nuclear translocation of γ-catenin from the desmosome. The identified new pathway greatly helps to comprehend S100A11\'s nature in colorectal cancers and others.
摘要：
汇编的证据表明,高水平的S100A11表达与各种癌症物种密切相关。与其他地方报告的结果一致，我们还发现S100A11在鳞状细胞癌中高表达，间皮瘤,和胰腺癌，当分泌到细胞外液中时，在癌症进展中起着至关重要的作用。这些研究都集中在S100A11的细胞外作用上。然而,大部分S100A11仍然存在于癌细胞中，尽管S100A11在癌细胞中的细胞内作用尚未完全阐明。因此，我们旨在研究S100A11在癌细胞中的功能，主要关注结直肠癌细胞，其S100A11在细胞中大量存在，并且对该蛋白的癌症研究仍然很少。我们的努力表明，S100A11的过表达促进增殖和迁移，下调反过来抑制了这些癌症行为。为了阐明细胞内S100A11如何帮助癌细胞活化，我们试图鉴定S100A11结合蛋白，在内膜中产生新的结合伴侣，其中许多是桥粒蛋白。我们的分子方法定义了S100A11调节DSG1的表达水平，DSG1是桥粒的组成蛋白，S100A11通过促进γ-连环蛋白从桥粒的核易位激活TCF途径。确定的新通路极大地有助于理解S100A11在结直肠癌和其他癌症中的性质。
