Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, China.
Department of Colorectal and Anal Surgery, the Second Hospital, Jilin University, Changchun, China.
Appl Biochem Biotechnol. 2024 Apr;196(4):2122-2136. doi: 10.1007/s12010-023-04664-x. Epub 2023 Jul 20.
Protein zero related (PZR) serves as a substrate and anchor protein for SHP-2, the product of the proto-oncogene PTPN11 that is frequently mutated in cancers. The expression level of PZR is elevated in various cancers, which is correlated with an unfavorable prognosis. The role of PZR in lung cancer is not fully studied. To investigate how PZR affects signaling pathways involved in LUAD development, we utilized the CRISPR technology to knock out PZR expression in SPC-A1 lung adenocarcinoma cells and then conducted RNA sequencing to profile the transcriptome. Our results showed that 226 genes exhibited differential expressions in PZR-knockout SPC-A1 cells vs wild-type cells. Many of the genes encode proteins involved in cell adhesion, migration, actin cytoskeleton organization, and regulation of cell shape. Furthermore, our experimental data showed that PZR-knockout SPC-A1 cells displayed faster attachment to tissue culture dishes and slower detachment from the dishes upon EDTA treatment. The data suggest an important role of PZR in cell-matrix interaction and may provide new insights into the signaling events that regulate cancer development.
蛋白零相关(PZR)是 SHP-2 的底物和锚定蛋白,SHP-2 是原癌基因 PTPN11 的产物,该基因在癌症中经常发生突变。PZR 的表达水平在各种癌症中升高,与预后不良相关。PZR 在肺癌中的作用尚未完全研究清楚。为了研究 PZR 如何影响 LUAD 发展相关的信号通路,我们利用 CRISPR 技术敲除 SPC-A1 肺腺癌细胞中的 PZR 表达,然后进行 RNA 测序以分析转录组。我们的结果表明,PZR 敲除 SPC-A1 细胞与野生型细胞相比,有 226 个基因表现出差异表达。许多基因编码参与细胞黏附、迁移、肌动蛋白细胞骨架组织和细胞形态调节的蛋白质。此外,我们的实验数据表明,PZR 敲除 SPC-A1 细胞在组织培养皿上的附着速度更快,在用 EDTA 处理时从培养皿上的脱落速度更慢。这些数据表明 PZR 在细胞-基质相互作用中起着重要作用,并可能为调节癌症发展的信号事件提供新的见解。