Acetylated-PPARγ expression is regulated by different P53 genotypes associated with the adipogenic differentiation of polyploid giant cancer cells with daughter cells

Abstract

Objective: Polyploid giant cancer cells (PGCCs) with daughter cells express epithelial–mesenchymal transition (EMT)-associated proteins. Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells. In this study, we elucidated the potential for, and underlying mechanism of, adipogenic differentiation of PGCCs with daughter cells (PDCs). Methods: Cobalt chloride was used to induce PGCC formation in HEY (wild-type P53) and MDA-MB-231 (mutant P53) cells; these cells were then cultured in adipogenic differentiation medium. Oil red O staining was used to confirm adipogenic differentiation, and the cell cycle was detected with flow cytometry. The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation. Animal xenograft models were used to confirm the adipogenic differentiation of PDCs. Results: PDCs transdifferentiated into functional adipocytes. Two different cell cycle distributions were observed in PDCs after adipogenic differentiation. The expression levels of PPARγ, Ace-PPARγ, and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation. Ace-PPARγ and FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown. A485 treatment increased Ace-P53, Ace-PPARγ, and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53. In MDA-MB-231 PDCs, A485 treatment decreased Ace-P53, Ace-PPARγ, and FABP4 expression. Animal experiments also confirmed the adipogenic differentiation of PDCs. Conclusions: Acetylation of P53 and PPARγ plays an important role in the adipogenic differentiation of PDCs.