Tumor Protein D53 (TPD53): Involvement in Malignant Transformation of Low-Malignant Oral Squamous Cell Carcinoma...

Background/Objectives: The tumor protein D52 (TPD52) family includes TPD52, TPD53, TPD54, and TPD55. The balance between TPD52 and TPD54 expression plays an important role in high-malignant oral squamous cell carcinoma (OSCC) cells. However, the relationship between TPD53 and OSCC cells (particularly low-malignant OSCC cells) remains unclear. In the present study, we investigated the role of TPD53 in the malignant transformation of low-malignant OSCC cells. Methods: Temporal changes in the expression of TPD52 family members at the protein and mRNA levels in OSCC cells and normal human epidermal keratinocytes (NHEK) were examined. Results: The mRNA expression of TPD53 increased in HSC-3 and HSC-4 cells in a time-dependent manner. Similar results for protein expression were observed. The effects of TPD53 on anchorage-dependent and anchorage-independent proliferation, cell cycle, invasion and migration, epithelial-mesenchymal transition (EMT), and matrix metalloproteinase (MMP) activities in HSC-3 and HSC-4 cells were assayed. Finally, using the HSC-3-xenograft-nude-mice model, these effects were examined in vivo. Overexpression of TPD53 increased cell viability and the percentage of cells in the S phase. Furthermore, overexpression of TPD53 increased cell invasion, migration, and MMP activities, regardless of its effect on EMT. Notably, these effects were more pronounced in HSC-3 than in HSC-4 cells. Overexpression of TPD53 enhanced tumor formation and growth in mouse xenografts, corroborating the results of in vitro experiments. Conclusions: The present study revealed novel and important functions of TPD53 in the proliferation and invasion of low-malignant OSCC cells.