title: Gene regulation by cohesin in cancer: is the ring an unexpected party to proliferation?
abstract: Cohesin is a multisubunit protein complex that plays an integral role in sister chromatid cohesion, DNA repair, and meiosis. Of significance, both over- and underexpression of cohesin are associated with cancer. It is generally believed that cohesin dysregulation contributes to cancer by leading to aneuploidy or chromosome instability. For cancers with loss of cohesin function, this idea seems plausible. However, overexpression of cohesin in cancer appears to be more significant for prognosis than its loss. Increased levels of cohesin subunits correlate with poor prognosis and resistance to drug, hormone, and radiation therapies. However, if there is sufficient cohesin for sister chromatid cohesion, overexpression of cohesin subunits should not obligatorily lead to aneuploidy. This raises the possibility that excess cohesin promotes cancer by alternative mechanisms. Over the last decade, it has emerged that cohesin regulates gene transcription. Recent studies have shown that gene regulation by cohesin contributes to stem cell pluripotency and cell differentiation. Of importance, cohesin positively regulates the transcription of genes known to be dysregulated in cancer, such as Runx1, Runx3, and Myc. Furthermore, cohesin binds with estrogen receptor α throughout the genome in breast cancer cells, suggesting that it may be involved in the transcription of estrogen-responsive genes. Here, we will review evidence supporting the idea that the gene regulation function of cohesin represents a previously unrecognized mechanism for the development of cancer.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Rhodes
authors.forename: Miranda
authors.initials: M
authors.lastname: McEwan
authors.forename: Julia A
authors.initials: JA
authors.lastname: Horsfield
mesh_terms: D000782:Aneuploidy; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D043171:Chromosomal Instability / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D004260:DNA Repair; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D039904:Pluripotent Stem Cells; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins