Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors
Summary: Loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC). We identify Rad21 as a gatekeeper o...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714009280 |
| _version_ | 1819198815550308352 |
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| author | Huiling Xu Yuqian Yan Siddhartha Deb Danny Rangasamy Markus Germann Jordane Malaterre Noreen C. Eder Robyn L. Ward Nicholas J. Hawkins Richard W. Tothill Long Chen Neil J. Mortensen Stephen B. Fox Michael J. McKay Robert G. Ramsay |
| author_facet | Huiling Xu Yuqian Yan Siddhartha Deb Danny Rangasamy Markus Germann Jordane Malaterre Noreen C. Eder Robyn L. Ward Nicholas J. Hawkins Richard W. Tothill Long Chen Neil J. Mortensen Stephen B. Fox Michael J. McKay Robert G. Ramsay |
| author_sort | Huiling Xu |
| collection | DOAJ |
| description | Summary: Loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC). We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1) retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer. : Rad21 holds the cohesin complex together as part of its role in chromosome partitioning and DNA repair. Xu et al. identify Rad21 as a key mediator of Apc gene heterozygous loss, the event initiating intestinal tumorigenesis. The subsequent activation of the Wnt pathway further induces Rad21, global gene dysregulation, chromosome instability, and pervasive retrotransposon activation. |
| first_indexed | 2024-12-23T03:06:26Z |
| format | Article |
| id | doaj.art-b13a4e1b60aa4ffea363bce846f041a5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T03:06:26Z |
| publishDate | 2014-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b13a4e1b60aa4ffea363bce846f041a52022-12-21T18:02:18ZengElsevierCell Reports2211-12472014-12-019517811797Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal TumorsHuiling Xu0Yuqian Yan1Siddhartha Deb2Danny Rangasamy3Markus Germann4Jordane Malaterre5Noreen C. Eder6Robyn L. Ward7Nicholas J. Hawkins8Richard W. Tothill9Long Chen10Neil J. Mortensen11Stephen B. Fox12Michael J. McKay13Robert G. Ramsay14Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre (PMCC), East Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3000, Australia; Department of Pathology, The University of Melbourne, Parkville, VIC 3000, AustraliaDifferentiation and Transcription Laboratory, Peter MacCallum Cancer Centre (PMCC), East Melbourne, VIC 3002, AustraliaPathology Department, PMCC, East Melbourne, VIC 3002, Australia; Victorian Cancer Biobank, Carlton, VIC 3053, AustraliaJohn Curtin School of Medical Research, The Australian National University, Acton, ACT 2601, AustraliaDifferentiation and Transcription Laboratory, Peter MacCallum Cancer Centre (PMCC), East Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3000, AustraliaDifferentiation and Transcription Laboratory, Peter MacCallum Cancer Centre (PMCC), East Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3000, AustraliaDifferentiation and Transcription Laboratory, Peter MacCallum Cancer Centre (PMCC), East Melbourne, VIC 3002, AustraliaPrince of Wales Clinical School, University of New South Wales (UNSW), Sydney, NSW 2052, AustraliaSchool of Medical Sciences, UNSW, Sydney, NSW 2052, AustraliaCancer Therapeutics Program, Cancer Research Division, PMCC, East Melbourne, VIC 3002, AustraliaJohn Curtin School of Medical Research, The Australian National University, Acton, ACT 2601, AustraliaDepartment of Colorectal Surgery, Oxford University Hospitals, Oxford Cancer Centre, Churchill Hospital, Oxford OX3 7LJ, UKDepartment of Pathology, The University of Melbourne, Parkville, VIC 3000, Australia; Pathology Department, PMCC, East Melbourne, VIC 3002, AustraliaUniversity of Sydney and North Coast Cancer Institute, Lismore, NSW 2480, AustraliaDifferentiation and Transcription Laboratory, Peter MacCallum Cancer Centre (PMCC), East Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3000, Australia; Corresponding authorSummary: Loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC). We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1) retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer. : Rad21 holds the cohesin complex together as part of its role in chromosome partitioning and DNA repair. Xu et al. identify Rad21 as a key mediator of Apc gene heterozygous loss, the event initiating intestinal tumorigenesis. The subsequent activation of the Wnt pathway further induces Rad21, global gene dysregulation, chromosome instability, and pervasive retrotransposon activation.http://www.sciencedirect.com/science/article/pii/S2211124714009280 |
| spellingShingle | Huiling Xu Yuqian Yan Siddhartha Deb Danny Rangasamy Markus Germann Jordane Malaterre Noreen C. Eder Robyn L. Ward Nicholas J. Hawkins Richard W. Tothill Long Chen Neil J. Mortensen Stephen B. Fox Michael J. McKay Robert G. Ramsay Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors Cell Reports |
| title | Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors |
| title_full | Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors |
| title_fullStr | Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors |
| title_full_unstemmed | Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors |
| title_short | Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors |
| title_sort | cohesin rad21 mediates loss of heterozygosity and is upregulated via wnt promoting transcriptional dysregulation in gastrointestinal tumors |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714009280 |
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