Abstract:
CD133 is an extensively studied marker of the most malignant tumor cell population,
designated as cancer stem cells (CSCs). However, the function of this glycoprotein and its involvement
in cell regulatory cascades are still poorly understood. Here we show a positive correlation between
the level of CD133 plasma membrane expression and the proliferative activity of cells of the Caco-2,
HT-29, and HUH7 cancer cell lines. Despite a substantial difference in the proliferative activities of
cell populations with different levels of CD133 expression, transcriptomic and proteomic profiling
revealed only minor distinctions between them. Nonetheless, a further in silico assessment of the
differentially expressed transcripts and proteins revealed 16 proteins that could be involved in the
regulation of CD133 expression; these were assigned ranks reflecting the apparent extent of their
involvement. Among them, the TRIM28 transcription factor had the highest rank. The prominent
role of TRIM28 in CD133 expression modulation was confirmed experimentally in the Caco2 cell
line clones: the knockout, though not the knockdown, of the TRIM28 gene downregulated CD133.
These results for the first time highlight an important role of the TRIM28 transcription factor in the
regulation of CD133-associated cancer cell heterogeneity.