Department of Medical Oncology Center, Zhongshan City People's Hospital, 528403, Zhongshan City, Guangdong Province, P. R. China.
Cell Death Dis. 2022 Jul 21;13(7):633. doi: 10.1038/s41419-022-05087-y.
Uncontrolled growth, distant metastasis and chemoresistance are critical characteristics of pancreatic ductal adenocarcinoma (PDAC), and they result in high mortality; however, the mechanisms triggering these effects have not been fully investigated. In this study, we analysed a dataset in the Cancer Genome Atlas (TCGA) and identified PCDH1, a rarely studied transmembrane protein, as a novel prognostic marker in PDAC patients. We demonstrated that PCDH1 expression was upregulated in PDAC tissues, and its expression levels were associated with the depth of tumour invasion and lymph node metastasis. Patients with high PCDH1 levels showed poor overall survival (OS). We also investigated the biological significance of PCDH1 in PDAC cell growth, metastasis, and side population (SP) phenotype acquisition and explored the internal molecular mechanisms of PCDH1 action. Our results demonstrated that PCDH1 enhanced p65 nuclear localization by interacting with KPNB1, a well-characterized nuclear transporter, thereby activating the NF-κB signalling pathway and increasing its functional effects during PDAC progression. Hence, our results indicate that PCDH1 can be used as a negative prognostic marker and may be a potential therapeutic target for PDAC patients.
不受控制的生长、远处转移和化疗耐药性是胰腺导管腺癌（PDAC）的关键特征，这导致了高死亡率；然而，引发这些效应的机制尚未被充分研究。在本研究中，我们分析了癌症基因组图谱（TCGA）中的一个数据集，发现了一个很少被研究的跨膜蛋白 PCDH1，是 PDAC 患者的一个新的预后标志物。我们证明了 PCDH1 在 PDAC 组织中表达上调，其表达水平与肿瘤侵袭深度和淋巴结转移有关。PCDH1 水平高的患者总生存期（OS）较差。我们还研究了 PCDH1 在 PDAC 细胞生长、转移和侧群（SP）表型获得中的生物学意义，并探讨了 PCDH1 作用的内部分子机制。我们的结果表明，PCDH1 通过与 KPNB1（一种特征明确的核转运蛋白）相互作用，增强了 p65 的核定位，从而激活了 NF-κB 信号通路，并在 PDAC 进展过程中增加了其功能效应。因此，我们的结果表明，PCDH1 可用作负预后标志物，并且可能是 PDAC 患者的潜在治疗靶点。
