{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:39Z","timestamp":1787029239016,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.","award":["17K09363"],"award-info":[{"award-number":["17K09363"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Although sessile serrated adenoma\/polyps (SSA\/Ps) may arise through a pathway different from the traditional adenoma\u2013carcinoma sequence, details of SSA\/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the \u03b2-catenin\/REG I\u03b1 axis in SSA\/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA\/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of \u03b2-catenin, REG I\u03b1 and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA\/P lesions (53.3%) were positive for Fn. Eighteen SSA\/P lesions (60%) showed \u03b2-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of \u03b2-catenin (87.5%) and higher REG I\u03b1 scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA\/P lesions expressing \u03b2-catenin in nuclei had significantly higher REG I\u03b1 scores and Ki67 labeling indices than those expressing \u03b2-catenin on cytomembranes. The REG I\u03b1 score was positively correlated with the Ki67 labeling index in SSA\/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear \u03b2-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA\/P lesions through promotion of \u03b2-catenin nuclear translocation and REG I\u03b1 expression.<\/jats:p>","DOI":"10.3390\/pathogens10040434","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T06:05:43Z","timestamp":1617689143000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of the \u03b2-Catenin\/REG I\u03b1 Axis in the Proliferation of Sessile Serrated Adenoma\/Polyps Associated with Fusobacterium nucleatum"],"prefix":"10.3390","volume":"10","author":[{"given":"Heihachiro","family":"Nishimura","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Fukui","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-1816","authenticated-orcid":false,"given":"Nobuhiko","family":"Ebisutani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1283-9009","authenticated-orcid":false,"given":"Toshihiko","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-932X","authenticated-orcid":false,"given":"Tadayuki","family":"Oshima","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Miwa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/359235a0","article-title":"APC mutations occur early during colorectal tumorigenesis","volume":"359","author":"Powell","year":"1992","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/01.pas.0000213313.36306.85","article-title":"Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points","volume":"30","author":"Yang","year":"2006","journal-title":"Am. 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