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 ...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-PPARγand 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 PPARγplays an important role in the adipogenic differentiation of PDCs.展开更多
In the past,contradictory statements have been made about the age of cancer genes.While phylostratigraphic studies suggest that cancer genes emerged during the transitional period from unicellularians(UC)to early meta...In the past,contradictory statements have been made about the age of cancer genes.While phylostratigraphic studies suggest that cancer genes emerged during the transitional period from unicellularians(UC)to early metazoans(EM),life cycle studies suggest that they arose earlier.This controversy could not be resolved.Phylostratigraphic methods use data from somatic tumor gene collections containing or lacking polyploidy genes(PGCC genes)and compare them to genes from evolutionary node taxa.I analyze whether the selected taxa are suitable to resolve the above contradiction or not.Both cancer and amoebae life cycles have a reproductive asexual germline that produces germline stem cells(GSCs)and somatic cell lines that cannot.When the germline loses its reproductive function,the soma-to-germ transition forms a new reproductive germline.The reproductive polyploidy of cancer is homologous to the reproductive polyploidy of unicellular cysts.PGCCs repair DNA defects,reorganize the involved genome architecture and produce new GSCs.The present study refutes the dogma of the early metazoan origin of cancer.Cancer has a unicellular life cycle that was adopted by early metazoans to rescue themselves from evolutionary dead ends.Early metazoans controlled the unicellular life cycle through suppressor and anti-suppressor genes that could suspend or reactivate it.They are the archetypes of tumor suppressor genes and oncogenes.Cells of mammalians and humans that reach a similar impasse as early metazoans can reactivate the conserved life cycle of unicellularians.展开更多
基金supported partly by grants from the National Natural Science Foundation of China(Grant Nos.82173283 and 82103088)the Foundation of the Committee on Science and Technology of Tianjin(Grant No.20JCYBJC01230)。
文摘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-PPARγand 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 PPARγplays an important role in the adipogenic differentiation of PDCs.
文摘In the past,contradictory statements have been made about the age of cancer genes.While phylostratigraphic studies suggest that cancer genes emerged during the transitional period from unicellularians(UC)to early metazoans(EM),life cycle studies suggest that they arose earlier.This controversy could not be resolved.Phylostratigraphic methods use data from somatic tumor gene collections containing or lacking polyploidy genes(PGCC genes)and compare them to genes from evolutionary node taxa.I analyze whether the selected taxa are suitable to resolve the above contradiction or not.Both cancer and amoebae life cycles have a reproductive asexual germline that produces germline stem cells(GSCs)and somatic cell lines that cannot.When the germline loses its reproductive function,the soma-to-germ transition forms a new reproductive germline.The reproductive polyploidy of cancer is homologous to the reproductive polyploidy of unicellular cysts.PGCCs repair DNA defects,reorganize the involved genome architecture and produce new GSCs.The present study refutes the dogma of the early metazoan origin of cancer.Cancer has a unicellular life cycle that was adopted by early metazoans to rescue themselves from evolutionary dead ends.Early metazoans controlled the unicellular life cycle through suppressor and anti-suppressor genes that could suspend or reactivate it.They are the archetypes of tumor suppressor genes and oncogenes.Cells of mammalians and humans that reach a similar impasse as early metazoans can reactivate the conserved life cycle of unicellularians.