Acquiring Metastatic Competence by Oral Squamous Cell Carcinoma Cells Is Associated with Differential Expression ofα-Tubulin Isoforms

[摘要] We performed comparative global proteomics analyses of patient-matched primary (686Tu) and metastatic (686Ln) OSCC cells. The metastatic OSCC 686Ln cells showed greaterin vitromigratory/invasive potential and distinct cell shape from their parental primary 686Tu cells. Ettan DIGE analysis revealed 1316 proteins spots in both cell lines with >85% to be quantitatively similar (<2 folds) between the two cell lines. However, two protein spots among four serial spots were highly dominant in 686Ln cells. Mass spectrometry sequencing demonstrated all four spots to beα-tubulin isotypes. Further analysis showed no significant quantitative difference in theα-tubulin between the two cell lines either at mRNA or protein levels. Thus, two distinct isoforms ofα-tubulin, probably due to posttranslational modification, were associated with metastatic 686Ln cells. Immunofluorescence demonstrated remarkable differences in the cytosolicα-tubulin distribution patterns between the two cells. In 686Tu cells,α-tubulin proteins formed a normal network composed of filaments. In contrast,α-tubulin in 686Ln cells exhibited only partial cytoskeletal distribution with the majority of the protein diffusely distributed within the cytosol. Sinceα-tubulin is critical for cell shape and mobility, our finding suggests a role ofα-tubulin isoforms in acquisition of metastatic phenotype and represents potential target for therapeutic intervention.

[学科分类] 肿瘤学