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Non-canonical WNT5A...
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Mehdawi, Lubna M.Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
(författare)
Non-canonical WNT5A signaling up-regulates the expression of the tumor suppressor 15-PGDH and induces differentiation of colon cancer cells
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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2016-08-01
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Wiley,2016
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15 s.
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:7d02dfba-db61-4b9d-95c4-d8e7aced1b64
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https://lup.lub.lu.se/record/7d02dfba-db61-4b9d-95c4-d8e7aced1b64URI
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https://doi.org/10.1016/j.molonc.2016.07.011DOI
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Språk:engelska
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Sammanfattning på:engelska
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The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme in prostaglandin E2 catabolism and is down-regulated in colorectal cancer (CRC) tissue. Canonical Wnt signaling is frequently elevated in colon cancers and has been shown to down-regulate 15-PGDH expression. Therefore, we have in the current study investigated if the non-canonical ligand WNT5A relates to increased expression of 15-PGDH in colon cancer cells. In the same cohort of patients, we demonstrated a parallel and significant loss of 15-PGDH and WNT5A protein expression in CRC tissues compared with matched normal colon tissues. Furthermore, patients with low 15-PGDH/WNT5A expression in their tumors showed reduced survival compared with patients with high 15-PGDH/WNT5A expression. To investigate if WNT5A signaling directly affects 15-PGDH expression, we performed in vitro analyses of colon cancer cells (HT-29 and Caco-2). Both cell lines, when treated with recombinant WNT5A (rWNT5A) or Foxy-5, a WNT5A-mimicking peptide, responded by increasing their expression of 15-PGDH mRNA and protein. Our investigations showed that rWNT5A and Foxy-5 induced this increased expression of 15-PGDH through reduced β-catenin signaling as well as increased JNK/AP-1 signaling in colon cancer cells. WNT5A signaling also induced increased 15-PGDH expression in a breast cancer cell line both in vitro and in vivo. In agreement, WNT5A signaling also increased the expression of the differentiation markers sucrose-isomaltase and mucin-2 in colon cancer cells. Our results show that WNT5A signaling regulates 15-PGDH expression, thus uncovering a novel mechanism by which WNT5A acts as a tumor suppressor and suggests that increased 15-PGDH expression could be used as an indicator of a positive response to Foxy-5 in patients treated with this WNT5A agonist.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Prasad, Chandra PrakashLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-cap
(författare)
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Ehrnström, RoyLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)pat-reh
(författare)
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Andersson, TommyLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)expp-tan
(författare)
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Sjölander, AnitaLund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)expp-asj
(författare)
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Cellpatologi, MalmöForskargrupper vid Lunds universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular Oncology: Wiley10:9, s. 1415-14291574-7891
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