The expanding role of yeast in cancer research and diagnosis: insights into the function of the oncosuppressors p53 and BRCA1/2

Abstract

When the glucose supply is high, despite the presence of oxygen, Saccharomyces cerevisiae uses fermentation as its main metabolic pathway and switches to oxidative metabolism only when this carbon source is limited. There are similarities between glucose-induced repression of oxidative metabolism of yeast and metabolic reprogramming of tumor cells. The glucose-induced repression of oxidative metabolism is regulated by oncogene homologues in yeast, such as RAS and Sch9p, the yeast homologue of Akt. Yeast also undergoes an apoptosis-like programmed cell death process sharing several features with mammalian apoptosis, including oxidative stress and a major role played by mitochondria. Evasion of apoptosis and sustained proliferative signaling are hallmarks of cancer. This, together with the possibility of heterologous expression of human genes in yeast, has allowed new insights to be obtained into the function of mammalian oncogenes/oncosuppressors. Here, we elaborate on the similarities between tumor and yeast cells underpinning the use of this model organism in cancer research. We also review the achievements obtained through heterologous expression in yeast of p53, BRCA1, and BRCA2, which are among the best-known cancer-susceptibility genes, with the aim of understanding their role in tumorigenesis. Yeast-cell-based functional assays for cancer genetic testing will also be dealt with.

Proteome and metabolome profiling of wild-type and YCA1 -knock-out yeast cells during acetic acid-induced programmed cell death

“…The results of this study expand the use of yeast as a model to study PCD pathways in normal and cancer-related conditions [81,82]. …”

Establishing a yeast-based screening system for discovery of human GLUT5 inhibitors and activators

“…For instance, yeast was used as a model system to study the mechanisms of neurodegenerative diseases 24 and cancer 25 . For the analysis of sugar transporters from various sources, yeast has proved an excellent model system.…”

The dominant-negative interplay between p53, p63 and p73: A family affair

“…Among the models used to study p53 family members, yeast has received much attention as it can be used to evaluate human p53 transcriptional activity using FASAY (Functional Analysis of Separated Alleles of p53 in Yeast) [58–60]. FASAY is based on engineered yeast strains whose genome contains a reporter gene which expression is driven by a specific p53 response element.…”