Cellular Prion Protein PrPC and Ecto-5′-Nucleotidase Are Markers of the Cellular Stress Response to Aneuploidy

Abstract

Aneuploidy is a hallmark of most human tumors, but the molecular physiology of aneuploid cells is not well characterized. In this study, we screened cell surface biomarkers of approximately 300 proteins by multiparameter flow cytometry using multiple aneuploid model systems such as cell lines, patient samples, and mouse models. Several new biomarkers were identified with altered expression in aneuploid cells, including overexpression of the cellular prion protein CD230/PrP and the immunosuppressive cell surface enzyme ecto-5'-nucleotidase CD73. Functional analyses associated these alterations with increased cellular stress. An increased number of CD73 cells was observed in confluent cultures in aneuploid cells relative to their diploid counterparts. An elevated expression in CD230/PrP was observed in serum-deprived cells in association with increased generation of reactive oxygen species. Overall, our work identified biomarkers of aneuploid karyotypes, which suggest insights into the underlying molecular physiology of aneuploid cells. .

Evolutionary Expression of HER2 Conferred by Chromosome Aneuploidy on Circulating Gastric Cancer Cells Contributes to Developing Targeted and Chemotherapeutic Resistance

“…Similarly, it is reasonable to speculate that aneuploid Chr8 with extra copies of chromosome in CTCs may have an impact on noncoding HER2 protein in a similar way. Moreover, it was observed that unique aneuploidy was able to facilitate tumorigenesis via generating phenotypic variants and to provide a growth advantage under selective pressure (35,(38)(39)(40). Indeed, in the present study we demonstrated that multiploid Chr8 contributed to phenotypic conversion from cHER2 À to cHER2 þ on CTCs, which is speculated to improve the cellular adaption of cHER2 þ CTCs against therapeutic pressure, and in turn to facilitate development of resistance to therapy.…”

Blocking Mitotic Exit of Ovarian Cancer Cells by Pharmaceutical Inhibition of the Anaphase-Promoting Complex Reduces Chromosomal Instability

“…CIN results from errors in DNA replication, DNA repair, or chromosomal mis-segregation [58]. CIN is of particular interest because it is associated with aggressive tumors, the acquisition of drug resistance, and poor patient prognosis [59], [60], [61], [62]. Multiple investigations described genome instability in ovarian cancer [63], [64], [65], which is characterized by gene copy number variations, rearranged genomes, structural variants, and single nucleotide variants.…”

The Cellular Prion Protein and the Hallmarks of Cancer

“…A second question is whether the expression of PrP C may afford protection against DNA damage. A major observation regarding the first point is the identification of cell surface PrP C as a marker of aneuploidy in a pan-cancer screening study [ 111 ]. The authors further reported an increase in PrP C levels in parental or aneuploid HCT116 colorectal cancer cells upon serum-deprivation, which they linked to oxidative stress, and showed that PrP C is protective against serum-deprivation-induced necrotic death [ 111 ].…”