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Inflammation suppre...
Inflammation suppresses DLG2 expression decreasing inflammasome formation
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- Keane, Simon (författare)
- Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Translational Medicine TRIM
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- Herring, Matthew (författare)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Infection Biology
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- Rolny, P. (författare)
- Division of Gastroenterology/Hepatology, Department of Medicine, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
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- Wettergren, Yvonne, 1957 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery,Department of Surgery, The Sahlgrenska Academy at University of Gothenburg, SU/Östra, Gothenburg, Sweden
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- Ejeskär, Katarina, 1969- (författare)
- Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Translational Medicine TRIM
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(creator_code:org_t)
- 2022-05-02
- 2022
- Engelska.
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 148:9, s. 2295-2311
- Relaterad länk:
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https://doi.org/10.1...
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https://his.diva-por... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Purpose Loss of expression of DLG2 has been identified in a number of cancers to contribute to the disease by resulting in increased tumor cell proliferation and poor survival. In light of the previous evidence that DLG2 alters the cell cycle and affects proliferation, combined with indications that DLG2 is involved in NLRP3 inflammasome axis we speculated that DLG2 has an immune function. So far, there is no data that clearly elucidates this role, and this study was designed to investigate DLG2 in inflammatory colon disease and in colon cancer as well as its impact on inflammasome induction. Methods The DLG2 expression levels were established in publicly available inflammation, colon cancer and mouse model datasets. The overexpression and silencing of DLG2 in colon cancer cells were used to determine the effect of DLG2 expression on the activation of the inflammasome and subsequent cytokine release. Results The expression of DLG2 is repressed in inflammatory colon diseases IBD and Ulcerative colitis as well as colorectal cancer tissue compared to healthy individuals. We subsequently show that induction with inflammatory agents in cell and animal models results in a biphasic alteration of DLG2 with an initial increase followed by an ensuing decrease. DLG2 overexpression leads to a significant increase in expression of IL1B, I kappa B zeta and BAX, components that result in inflammasome formation. DLG2 silencing in THP1 cells resulted in increased release of IL-6 into the microenvironment which once used to treat bystander COLO205 cells resulted in an increase in STAT3 phosphorylation and an increase proliferating cells and more cells in the G2/M phase. Restoration of DLG2 to the colon resulted in reduced AKT and S6 signaling. Conclusion DLG2 expression is altered in response to inflammation in the gut as well as colon cancer, resulting in altered ability to form inflammasomes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- DLG2
- Inflammasome
- NFKBIZ
- Ulcerative colitis
- Colon cancer
- kappa-b-zeta
- colorectal-cancer
- colon-cancer
- mutant p53
- cell
- genes
- proliferation
- apoptosis
- protein
- profile
- Oncology
- DLG2
- Translationell medicin TRIM
- Infection Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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