School of Medicine, Northwest University, Xi'an, Shaanxi 710069, China.
Department of Oncology Surgery, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi 710016, China.
Cell Mol Biol (Noisy-le-grand). 2024 Jul 28;70(7):100-105. doi: 10.14715/cmb/2024.70.7.14.
Goosecoid (GSC), translated from a homeobox gene, is a protein that participates in metastasis of various cancers. Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies associated with a poor diagnosis and prognosis. To develop new treatment target or biomarker for PAAD, this study intended to assess the effects and the molecular mechanism of GSC on PAAD metastasis. The expressive discrepancy of GSC in PAAD and normal tissues/cells was compared by both the quantitative PCR and western blot. The effects of GSC silencing and GSC over-expression on PAAD cells and TGF-β signaling were proved by wound-healing assay, cell counting kit-8, Transwell assay and western blot. From the results, GSC mRNA and protein levels were enriched in PAAD cancer tissues and cells. GSC silencing prohibited metastasis of PAAD cells including the ability to invade, migrate and epithelial-mesenchymal transition (EMT), whereas GSC upregulation stimulated these cells behaviors above. GSC silencing reversed the effects on cellular processes induced by activation of the TGF-β pathway. Furthermore, silencing of GSC postponed tumor growth in xenograft model. In summary, GSC was abundantly expressed in PAAD, which activated the TGF-β pathway to enhance cell metastasis and tumor development.
Goosecoid（GSC），一种同源盒基因翻译的蛋白，参与多种癌症的转移。胰腺导管腺癌（PAAD）是与较差的诊断和预后相关的最致命的恶性肿瘤之一。为了开发治疗 PAAD 的新靶点或生物标志物，本研究旨在评估 GSC 对 PAAD 转移的影响及其分子机制。通过定量 PCR 和 Western blot 比较 GSC 在 PAAD 和正常组织/细胞中的表达差异。通过划痕愈合试验、细胞计数试剂盒-8、Transwell 试验和 Western blot 证实 GSC 沉默和 GSC 过表达对 PAAD 细胞和 TGF-β信号通路的影响。结果表明，GSC 在 PAAD 癌组织和细胞中的 mRNA 和蛋白水平较高。GSC 沉默抑制了 PAAD 细胞的转移，包括侵袭、迁移和上皮间质转化（EMT）的能力，而 GSC 的上调则刺激了这些细胞的上述行为。GSC 沉默逆转了 TGF-β 通路激活引起的细胞过程的影响。此外，GSC 的沉默在异种移植模型中推迟了肿瘤的生长。总之，GSC 在 PAAD 中大量表达，激活 TGF-β 通路增强细胞转移和肿瘤发展。
