Lin Cheng-Wei, Sun Min-Siou, Wu Han-Chung
Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei 115, Taiwan, R.O.C.
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, R.O.C.
Int J Oncol. 2014 Aug;45(2):710-8. doi: 10.3892/ijo.2014.2427. Epub 2014 May 8.
Metastasis-mediated death remains a major challenge in cancer treatment due to the lack of identifiable biomarkers for early diagnosis. Identifying tumor-specific biomarkers is critical for the development of diagnostic and therapeutic tools. In the present study, we found that podocalyxin-like 1 (PODXL), a cell surface glycoprotein, was overexpressed in cancer tissues and was upregulated in lymph node metastatic tumor cells. The expression of PODXL was associated with the migratory ability of human oral squamous cell carcinoma (OSCC). Knockdown of PODXL by small hairpin RNA in the SAS OSCC cell line reduced tumor migration and invasion, and inhibited cell proliferation and colony formation. Suppression of PODXL resulted in downregulation of focal adhesion kinase (FAK) and paxillin phosphorylation. PODXL silencing inhibited filopodia formation, and suppressed F-actin and cortactin colocalization. In addition, PODXL expression was associated with the DNA methylation status, and treatment with the DNA methyltransferase inhibitor 5-aza-deoxycytidine increased the PODXL transcriptional level. Moreover, DNA microarray analysis data revealed that suppression of PODXL significantly affected subsets of genes associated with extracellular matrix organization, the epithelial-mesenchymal transition, and the expression of metastasis-related cytokines. Collectively, these data showed that the overexpression of PODXL may be associated with tumor aggressiveness and that PODXL could be a diagnostic biomarker for metastatic OSCC.
由于缺乏用于早期诊断的可识别生物标志物，转移介导的死亡仍然是癌症治疗中的一个主要挑战。识别肿瘤特异性生物标志物对于诊断和治疗工具的开发至关重要。在本研究中，我们发现细胞表面糖蛋白足突融合蛋白样1（PODXL）在癌组织中过表达，并且在淋巴结转移瘤细胞中上调。PODXL的表达与人类口腔鳞状细胞癌（OSCC）的迁移能力相关。在SAS OSCC细胞系中通过小发夹RNA敲低PODXL可减少肿瘤迁移和侵袭，并抑制细胞增殖和集落形成。PODXL的抑制导致粘着斑激酶（FAK）和桩蛋白磷酸化的下调。PODXL沉默抑制丝状伪足形成，并抑制F-肌动蛋白和皮层肌动蛋白的共定位。此外，PODXL表达与DNA甲基化状态相关，用DNA甲基转移酶抑制剂5-氮杂-脱氧胞苷处理可提高PODXL转录水平。此外，DNA微阵列分析数据显示，PODXL的抑制显著影响与细胞外基质组织、上皮-间质转化以及转移相关细胞因子表达相关的基因子集。总体而言，这些数据表明PODXL的过表达可能与肿瘤侵袭性相关，并且PODXL可能是转移性OSCC的诊断生物标志物。
