Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.
Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Gastric Cancer. 2019 Jan;22(1):48-59. doi: 10.1007/s10120-018-0833-y. Epub 2018 May 10.
Podocalyxin-like 1 (PODXL) was reported to be closely associated with the development of various cancers, yet its functional roles and molecular mechanisms remain vague. The aim of our study was to investigate the clinical significance, biological function and molecular mechanism of PODXL in gastric cancer (GC).
The level of PODXL in GC tissues was detected applying GC tissues microarray, fresh GC tissues and public database (Oncomine). The invasion, metastasis and tumorigenesis role of PODXL were performed in vitro and in vivo. The correlations between KLF4 and PODXL was determined in GC tissues microarray and fresh GC tissues, and the molecular regulatory mechanism between KLF4 and PODXL was explored in vitro.
The high level of PODXL was detected in GC tissues with advanced T stage, lymph node metastasis, Union for International Cancer Control stage and poor differentiation. And Cox proportional hazards model revealed that PODXL can serve as an independent prognostic indicator for disease-free survival and overall survival of GC patients. Moreover, downregulation of PODXL could inhibit EMT and reduce invasion and metastasis in vitro as well as tumorigenesis in vivo. Additionally, our findings showed that PODXL may be a significant downstream target of KLF4.
KLF4/PODXL signaling pathway assumes an irreplaceable role in tumorigenesis, invasion and metastasis of human GC and PODXL serves as an independent prognostic indicator for GC patients.
Podocalyxin-like 1（PODXL）被报道与多种癌症的发展密切相关，但它的功能作用和分子机制仍不清楚。我们的研究旨在探讨 PODXL 在胃癌（GC）中的临床意义、生物学功能和分子机制。
应用 GC 组织微阵列、新鲜 GC 组织和公共数据库（Oncomine）检测 PODXL 在 GC 组织中的水平。在体外和体内研究了 PODXL 的侵袭、转移和致瘤作用。在 GC 组织微阵列和新鲜 GC 组织中确定了 KLF4 和 PODXL 之间的相关性，并在体外探讨了 KLF4 和 PODXL 之间的分子调控机制。
GC 组织中 PODXL 水平高与 T 分期较晚、淋巴结转移、国际抗癌联盟分期和分化不良有关。Cox 比例风险模型显示，PODXL 可作为 GC 患者无病生存和总生存的独立预后指标。此外，下调 PODXL 可抑制 EMT，并减少体外侵袭和转移以及体内肿瘤发生。此外，我们的研究结果表明，PODXL 可能是 KLF4 的一个重要下游靶标。
KLF4/PODXL 信号通路在人类 GC 的发生、侵袭和转移中起着不可替代的作用，PODXL 可作为 GC 患者的独立预后指标。
