Dual role of sprouty2 as an inhibitor of RAS/ERK‐driven proliferation and a promoter of cancer invasion in KRAS wild‐type colorectal cancer
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Le résumé fourni par la source
Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo. We performed SPRY2 immunohistochemical staining in 143 CRC specimens and analyzed the staining results with various clinicopathological characteristics in relation to KRAS mutation status. SPRY2 knockdown in Caco-2 cells carrying the wild-type (WT) KRAS gene upregulated phosphorylated ERK (p-ERK) levels and increased cell proliferation in vitro, but inhibited cell invasion. However, SPRY2 knockdown in SW480 cells (activating KRAS mutant) or Caco-2 cells transfected with KRAS-mutant plasmid did not significantly alter p-ERK levels, cell proliferation, or invasion. The xenografts of SPRY2-knockdown Caco-2 cells were larger with less deep muscle invasion than those of control cells. The clinical cohort study revealed a positive association of SPRY2 protein expression with pT status, lymphovascular invasion, and perineural invasion in KRAS-WT CRCs. However, the associations were not observed in KRAS-mutant CRCs. Interestingly, high SPRY2 expression was related to shorter cancer-specific survival in both KRAS-WT and KRAS-mutant CRC patients. Our study demonstrated the dual role of SPRY2 as an inhibitor of RAS/ERK-driven proliferation and as a promoter of cancer invasion in KRAS-WT CRC. SPRY2 may promote the invasion and progression of KRAS-WT CRC, and might also enhance KRAS-mutant CRC progression through pathways other than invasion.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Dual role of sprouty2 as an inhibitor of RAS/ERK‐driven proliferation and a promoter of cancer invasion in KRAS wild‐type colorectal cancer
- Date Crossref
- 04/04/2023
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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National Cheng Kung University Hospital Department of Pathology pays non établi dans la noticeÉtablissement de santé
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National Cheng Kung University pays non établi dans la noticeUniversité ou école supérieure
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National Health Research Institutes pays non établi dans la noticeOrganisation à but non lucratif
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College of Medicine Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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College of Electrical Engineering and Computer Science pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Cancer Research pays non établi dans la noticeStructure de recherche
Department of Pathology — National Cheng Kung University Hospital, National Cheng Kung University et National Health Research Institutes, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.