The Many and Essential Roles of the Cohesin Complex in Colorectal Carcinogenesis
Event details
| Date | 21.04.2015 |
| Hour | 12:00 › 13:00 |
| Speaker | Prof. Robert Ramsay, Sir Peter MacCallum Department of Oncology, The Unversity of Melbourne, Australia |
| Location | |
| Category | Conferences - Seminars |
Abstract:
We have identified cohesin, RAD21 as a gatekeeper of tumor suppressor gene loss of heterozygosity (LOH) and as a direct b-catenin target gene. Accordingly Wnt pathway activation drives RAD21 expression in human colorectal cancer and high RAD21 is further associated with treatment refractory disease. Genome-wide analyses identified RAD21 as a key Polymerase 2 transcriptional regulator of critical colorectal cancer genes including stem cell genes and most unexpectedly repetitive elements including LINE-1 (L1) retrotransposons. Indeed, RAD21 re-activates transcription of normally silenced L1 expression in human cancer leading to associated chromosomal instability. Very recent work now shows a strong association between RAD21 and a second class of repetitive genes, the rDNA clusters transcribed by Polymerase 1. These finding emphasize the diverse engagement of cohesins in a broad spectrum of transcriptional activities that are subverted in cancer.
Additional information:
Besides his latest research on the mechanisms of genomic instability in colorectal cancer presented here, Rob has a long lasting expertise on signalling pathways involved in intestinal stem cell biology and tumorigenesis. In this field he has contributed substantial studies on the roles of WNT, CSF1 and, especially, the MYB proto-oncogene, latter of which he has further successfully used as a vaccination target in colorectal cancer.
People interested in having a meeting with Rob about work presented here or any other of his studies, please contact [email protected] to set up a schedule
We have identified cohesin, RAD21 as a gatekeeper of tumor suppressor gene loss of heterozygosity (LOH) and as a direct b-catenin target gene. Accordingly Wnt pathway activation drives RAD21 expression in human colorectal cancer and high RAD21 is further associated with treatment refractory disease. Genome-wide analyses identified RAD21 as a key Polymerase 2 transcriptional regulator of critical colorectal cancer genes including stem cell genes and most unexpectedly repetitive elements including LINE-1 (L1) retrotransposons. Indeed, RAD21 re-activates transcription of normally silenced L1 expression in human cancer leading to associated chromosomal instability. Very recent work now shows a strong association between RAD21 and a second class of repetitive genes, the rDNA clusters transcribed by Polymerase 1. These finding emphasize the diverse engagement of cohesins in a broad spectrum of transcriptional activities that are subverted in cancer.
Additional information:
Besides his latest research on the mechanisms of genomic instability in colorectal cancer presented here, Rob has a long lasting expertise on signalling pathways involved in intestinal stem cell biology and tumorigenesis. In this field he has contributed substantial studies on the roles of WNT, CSF1 and, especially, the MYB proto-oncogene, latter of which he has further successfully used as a vaccination target in colorectal cancer.
People interested in having a meeting with Rob about work presented here or any other of his studies, please contact [email protected] to set up a schedule
Practical information
- Informed public
- Free
Organizer
Contact
- Markus Germann