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Podocalyxin-like 1 is associated with tumor aggressiveness and metastatic gene expression in human oral squamous cell carcinoma.
- Source :
-
International journal of oncology [Int J Oncol] 2014 Aug; Vol. 45 (2), pp. 710-8. Date of Electronic Publication: 2014 May 08. - Publication Year :
- 2014
-
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.
- Subjects :
- Blotting, Western
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell metabolism
Cell Line, Tumor
DNA Methylation
Fluorescent Antibody Technique
Gene Knockdown Techniques
Humans
Immunohistochemistry
Mouth Neoplasms genetics
Mouth Neoplasms metabolism
Neoplasm Invasiveness
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
RNA, Small Interfering
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sialoglycoproteins genetics
Transcriptome
Biomarkers, Tumor analysis
Carcinoma, Squamous Cell pathology
Mouth Neoplasms pathology
Sialoglycoproteins biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 45
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24821609
- Full Text :
- https://doi.org/10.3892/ijo.2014.2427