Laboratory of Molecular Orthopaedics, Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital, Beijing, P. R. China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Cancer Med. 2023 Feb;12(4):4510-4520. doi: 10.1002/cam4.5192. Epub 2022 Sep 1.
Cancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell-like properties in lung cancer.
Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo.
By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell-like properties, including cell viability, invasion, migration, self-renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of β-catenin and activated Wnt/β-catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and β-catenin. Wnt/β-catenin pathway inhibitor blocked the Palladin-induced enhancement of sphere-forming.
Palladin might act as an oncogene by promoting CSCs-like properties and tumorigenicity of NSCLC cells via the Wnt/β-catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs.
癌症干细胞（CSCs）是导致耐药性、癌症复发和转移的原因。在这里，我们报告了首次分析肺癌中 Palladin 表达及其对干细胞样特性的影响。
使用组织微阵列分析 Palladin 表达及其与预后的关系。免疫荧光（IF）、流式荧光分析和 Western blot 用于检测 6 种 NSCLC 细胞系中的 Palladin 表达。评估细胞表型和耐药性。构建异种移植模型以确认 Palladin 在体内的作用。
通过使用组织微阵列，鉴定出 Palladin 在细胞质中高度表达，特别是在 NSCLC 的细胞质膜中，其高表达与预后不良相关。Palladin 广泛表达并富集在球体细胞中。体外和体内研究表明，Palladin 促进了干细胞样特性，包括细胞活力、侵袭、迁移、自我更新能力、紫杉醇耐药性和致瘤性。Western blot 显示 Palladin 促进了β-catenin 的积累并激活了 Wnt/β-catenin 信号通路。组织微阵列分析进一步证实了 Palladin 与β-catenin 之间的正相关。Wnt/β-catenin 通路抑制剂阻断了 Palladin 诱导的球体形成增强。
Palladin 可能通过激活 Wnt/β-catenin 信号通路促进 NSCLC 细胞的 CSCs 样特性和致瘤性，从而发挥癌基因的作用。此外，鉴定出 Palladin 具有作为 LCSCs 鉴定的细胞表面标志物的潜力。这些发现为开发针对 LCSCs 的潜在靶向药物提供了可能的目标。
