PHRF1 Promotes Cell Invasion by Modulating SOX4 Expression in Colorectal Cancer HCT116-p53 Cells.

Background/aim: PHD and RING finger domain-containing protein 1 (PHRF1) ubiquitinates TGIP (TG-interacting protein) and redistributes cPML (cytoplasmic variant of PML) to the cytoplasm to enhance TGF-β signaling by. It is unclear whether PHRF1 affects invasion and survival when both mutations of the activated oncogene Kras and inactivation of the tumor suppressor p53 are present.

Materials And Methods: We knockout PHRF1 expression using Crispr-Cas9 editing in HCT116-p53 (KrasG13D/p53) cells and analyzed the expression profile in HCT116-p53PHRF1 cells.

Results: In contrast to lung cancer A549 (KrasG12S/p53wt) cells, the expression of Zeb1, a transcription factor for epidermal-mesenchymal transition (EMT), was not affected in PHRF1-knockout HCT116 p53 cells. Instead, SOX4 displayed a significant contribution to the impaired invasion in HCT116-p53PHRF1 cells. Mechanistically, the C-terminal SRI domain of PHRF1 was required for both transwell invasion and SOX4 expression. The reintroduction of SOX4 into HCT116-p53 PHRF1 cells partially restored their invasive capability.

Conclusion: This study sheds light on the role of PHRF1 in the invasion of colorectal cancer HCT116-p53 cells, which harbor the oncogenic KrasG13D mutation and lack p53. These findings provide novel insights regarding the role of PHRF1 in invasion by modulating SOX4 expression in colorectal cancer HCT116-p53 cells.