PHRF1 Promotes Cell Invasion by Modulating SOX4 Expression in Colorectal Cancer HCT116-p53-/- Cells.
Anticancer Res
; 43(12): 5437-5446, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-38030167
ABSTRACT
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-ß 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 ANDMETHODS:
We knockout PHRF1 expression using Crispr-Cas9 editing in HCT116-p53-/- (KrasG13D/p53-/-) cells and analyzed the expression profile in HCT116-p53-/-PHRF1-/- 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-p53-/-PHRF1-/- 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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Fatores de Transcrição SOXC
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article