Department of Anatomy-Histology-Embryology, Medical School, University of Patras, 26504, Patras, Greece.
Department of General Biology, Medical School, University of Patras, 26504, Patras, Greece.
Clin Exp Med. 2023 Jul;23(3):871-885. doi: 10.1007/s10238-022-00847-8. Epub 2022 Jun 21.
Ras suppressor-1 (RSU1), originally described as a suppressor of Ras oncogenic transformation, localizes to focal adhesions interacting with the ILK-PINCH-PARVIN (IPP) complex that exerts a well-established oncogenic role in cancer. However, RSU1 implication in lung cancer is currently unknown. Our study aims to address the role of RSU1 in lung adenocarcinoma (LUADC). We here show that RSU1 protein expression by immunohistochemistry is downregulated in LUADC human tissue samples and represents a significant prognostic indicator. In silico analysis of gene chip and RNA seq data validated our findings. Depletion of RSU1 by siRNA in lung cancer cells promotes anchorage-independent cell growth, cell motility and epithelial to mesenchymal transition (EMT). Silencing of RSU1 also alters IPP complex expression in lung cancer cells. The p29 RSU1 truncated isoform is detected in lung cancer cells, and its expression is downregulated upon RSU1 silencing, whereas it is overexpressed upon ILK overexpression. These findings suggest that RSU1 exerts a tumor suppressive role with prognostic significance in LUADC.
Ras 抑制因子-1（RSU1）最初被描述为 Ras 致癌转化的抑制剂，它定位于与 ILK-PINCH-PARVIN（IPP）复合物相互作用的焦点粘连中，该复合物在癌症中具有明确的致癌作用。然而，RSU1 在肺癌中的作用尚不清楚。我们的研究旨在探讨 RSU1 在肺腺癌（LUADC）中的作用。我们在这里显示，RSU1 蛋白表达通过免疫组织化学在 LUADC 人组织样本中下调，并代表一个重要的预后指标。基因芯片和 RNA 测序数据的计算机分析验证了我们的发现。用 siRNA 耗尽肺癌细胞中的 RSU1 可促进非锚定依赖性细胞生长、细胞迁移和上皮间质转化（EMT）。RSU1 的沉默还改变了肺癌细胞中 IPP 复合物的表达。在肺癌细胞中检测到 p29 RSU1 截断异构体，其表达在 RSU1 沉默时下调，而在 ILK 过表达时上调。这些发现表明 RSU1 在 LUADC 中具有肿瘤抑制作用和预后意义。
