Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability.
Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense DK-5000, Denmark. aynielsen@health.sdu.dk.
Aaraby Yoheswaran
AY
Nielsen
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense DK-5000, Denmark. mgjerstorff@health.sdu.dk.
Morten Frier
MF
Gjerstorff
D000818:Animals; D064108:Aurora Kinase C / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D000066630:Ectopic Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D005854:Germ Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011123:Polyploidy; D011485:Protein Binding; D011995:Recombination, Genetic; D013312:Stress, Physiological; D013573:Synaptonemal Complex / Q000378:metabolism; D013737:Testis / Q000378:metabolism*
D015513:Oncogene Proteins; D064108:Aurora Kinase C
cancer development; genomic instability; mitosis; mitotic fidelity; polyploidy; testis germ cell proteins