Department of Biochemistry and Molecular Biology, University of Indiana School of Medicine, Indianapolis, Indiana 46202-5122, USA.
Cancer Res. 2011 Mar 15;71(6):2203-11. doi: 10.1158/0008-5472.CAN-10-1995. Epub 2011 Feb 1.
The asymmetric organization of epithelial cells is a basic counter to cellular proliferation. However, the mechanisms whereby pro-growth pathways are modulated by intracellular factors that control cell shape are not well understood. This study demonstrates that the adaptor protein Amot, in addition to its established role in regulating cellular asymmetry, also promotes extracellular signal-regulated kinase 1 and 2 (ERK1/2)-dependent proliferation of mammary cells. Specifically, expression of Amot80, but not a mutant lacking its polarity protein interaction domain, enhances ERK1/2-dependent proliferation of MCF7 cells. Further, expression of Amot80 induces nontransformed MCF10A cells to overgrow as disorganized cellular aggregates in Matrigel. Conversely, Amot expression is required for proliferation of breast cancer cells in specific microenvironmental contexts that require ERK1/2 signaling. Thus, Amot is proposed to coordinate the dysregulation of cell polarity with the induction of neoplastic growth in mammary cells.
上皮细胞的不对称组织是细胞增殖的基本对策。然而，控制细胞形状的细胞内因子调节促生长途径的机制尚不清楚。本研究表明，衔接蛋白 Amot 除了在调节细胞不对称性方面的既定作用外，还促进了乳腺细胞中细胞外信号调节激酶 1 和 2（ERK1/2）依赖性增殖。具体而言，表达 Amot80，但不是缺乏其极性蛋白相互作用域的突变体，可增强 MCF7 细胞中 ERK1/2 依赖性增殖。此外，表达 Amot80 诱导非转化的 MCF10A 细胞在 Matrigel 中过度生长为组织无序的细胞聚集物。相反，Amot 的表达是乳腺癌细胞在需要 ERK1/2 信号的特定微环境背景下增殖所必需的。因此，Amot 被提议协调细胞极性的失调与乳腺细胞中肿瘤生长的诱导。
