Different P53 Genotypes Regulating Different Phosphorylation Sites and Subcellular Location of CDC25C Associated with the Formation of Polyploid Giant Cancer Cells

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2020 May 13

PMID 32393310

Citations 17

Authors

Kai Liu

Minying Zheng

Qi Zhao

Kexin Zhang

Zugui Li

Fangmei Fu

Hao Zhang

Jiaxing Du

Yuwei Li

Shiwu Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Our previous studies have confirmed that cobalt chloride (CoCl) can induce the formation of polyploid giant cancer cells (PGCCs), which is the key to the heterogeneity of solid tumors. PGCC formation is closely related to the abnormal expression of cell cycle-related proteins and cell fusion. In this study, we investigated the molecular mechanism of PGCCs formation by detecting the expression of cell cycle-related proteins in mutant and wild-type p53 cancer cell lines.

Methods: HEY, BT-549, SKOv3 and MDA-MB-231 cells were treated with CoCl and the cell cycle was detected by flow cytometry. The expression and subcellular localization of cell cycle-related proteins, kinases, and P53 were compared before and after CoCl treatment. Immunoprecipitation was used to analyze the interacting proteins of pCDC25C-Ser216 and pCDC25C-Ser198. The clinicopathologic significances of these cell cycle-related proteins and protein kinases expression were studied.

Results: CoCl induced the formation of PGCCs and G2/M arrest. CDC25C, cyclin B1, and CDK1 expressions after CoCl treatment were lower than that in control cells. Cytoplasmic CDC25C was degraded by ubiquitin-dependent proteasome. The expression of P53 and phosphokinases including CHK1, CHK2, PLK1, and Aurora A increased after CoCl treatment. The expression of pCDC25C-Ser216 and pCDC25C-Ser198 depended upon the genotype of p53. The expressions of cell cycle-related proteins and kinases gradually increased with the development of ovarian cancer and breast cancer.

Conclusion: CHK1, CHK2-pCDC25C-Ser216-cyclin B1-CDK1, and Aurora A-PLK1-pCDC25C-Ser198-cyclin B1-CDK1 signaling pathways may participate in the formation of PGCCs and different phosphorylation sites of CDC25C may be associated with the genotype of p53.

Citing Articles

Emerging Paradigms in Cancer Metastasis: Ghost Mitochondria, Vasculogenic Mimicry, and Polyploid Giant Cancer Cells.

Krotofil M, Tota M, Siednienko J, Donizy P Cancers (Basel). 2024; 16(20).

PMID: 39456632 PMC: 11506636. DOI: 10.3390/cancers16203539.

Correction: Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells.

Liu K, Zheng M, Zhao Q, Zhang K, Li Z, Fu F J Exp Clin Cancer Res. 2024; 43(1):229.

PMID: 39154162 PMC: 11329984. DOI: 10.1186/s13046-024-03155-z.

Cells in the Polyaneuploid Cancer Cell State are Pro-Metastatic.

Mallin M, Rolle L, Schmidt M, Priyadarsini Nair S, Zurita A, Kuhn P bioRxiv. 2024; .

PMID: 39071340 PMC: 11275908. DOI: 10.1101/2024.07.12.603285.

Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation.

Liu P, Wang L, Yu H Front Cell Dev Biol. 2024; 12:1410637.

PMID: 39055650 PMC: 11269155. DOI: 10.3389/fcell.2024.1410637.

Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.

Jiao Y, Yu Y, Zheng M, Yan M, Wang J, Zhang Y Clin Transl Med. 2024; 14(2):e1567.

PMID: 38362620 PMC: 10870057. DOI: 10.1002/ctm2.1567.

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