Podocalyxin-like 1 is associated with tumor aggressiveness and metastatic gene expression in human oral squamous cell carcinoma

Abstract

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.

Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL

“…PODXL was previously reported to enhance tumor aggressiveness in breast cancer, prostate cancer, oral squamous cell carcinoma and astrocytoma (56)(57)(58)(59). hsu et al reported PODXL-ebP50-ezrin molecular complex enhances the metastatic potential of renal cancer through recruiting RAC1 guanine nucleotide exchange factor, ARhgeF7 (60).…”

MicroRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma

“…74 In studies conducted with oral squamous cell carcinoma (OSCC) cells, podocalyxin-like 1 protein, a sialomucin, is needed for OSCC migratory, invasive, and proliferative properties. 75 Podocalyxin-like 1 protein promotes invadopodia formation by regulating cortactin phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1)/cell division cycle 42 (CDC42) activity. 76 In squamous cell carcinoma cells, podoplanin, a type 1 transmembrane glycoprotein, localizes to invadopodia-associated adhesion rings and serves an important role in the stabilization of invadopodia.…”

Involvement of Platelet–Tumor Cell Interaction in Immune Evasion. Potential Role of Podocalyxin-Like Protein 1

“…The overexpression of PCLP1 has been associated with a more aggressive phenotype and poor prognosis in numerous types of cancer, including breast, colorectal, prostate, bladder, ovarian cancer, renal carcinoma, and oral squamous cell carcinoma, which suggests an important role of this protein in cancer progression and metastasis, although the underlying mechanisms are poorly understood (62–69). PCLP1 is also overexpressed in blasts of acute leukemia, testicular tumor, hepatic carcinoma, astrocytic tumor, and small cell lung carcinoma (70–74).…”