scholarly journals Role of Clostridium perfringens Enterotoxin on YAP Activation in Colonic Sessile Serrated Adenoma/Polyps with Dysplasia

2020 ◽  
Vol 21 (11) ◽  
pp. 3840 ◽  
Author(s):  
Rina Fujiwara-Tani ◽  
Kiyomu Fujii ◽  
Shiori Mori ◽  
Shingo Kishi ◽  
Takamitsu Sasaki ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Clostridium Perfringens ◽  
Low Dose ◽  
Nuclear Translocation ◽  
Tubular Adenoma ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma ◽  
Clostridium Perfringens Enterotoxin ◽  
Intracellular Translocation ◽  
E Cadherin

Sessile serrated adenoma/polyp with dysplasia (SSA/P-D) is an SSA/P with cellular dysplasia and has a higher risk of progressing to colon carcinogenesis. Previously, we reported that tight junction impairment by Clostridium perfringens enterotoxin (CPE) leads to activation of the transcriptional co-activator yes-associated protein (YAP) in oral squamous cell carcinoma. Here, we investigated whether CPE activates YAP to promote the malignant progression of SSA/P. E-cadherin expression was lower in the 12 cases with SSA/P-D examined than that in normal mucosa, SSA/P, or tubular adenoma (TA). Furthermore, intracellular translocation of claudin-4 (CLDN4) and nuclear translocation of YAP were observed. The CPE gene was detected in DNA extracted from SSA/P-D lesions, but not in SSA/P or TA. Treatment of the rat intestinal epithelial cell line IEC6 with low-dose CPE resulted in intracellular translocation of CLDN4 to the cytoplasmic membrane. Cytoplasmic CLDN4 showed co-precipitation with transcriptional co-activator with PDZ-binding motif, zonula occludens (ZO)-1, large tumor suppressor, and mammalian Ste20-like. Additionally, YAP co-precipitated with ZO-2 under CPE treatment led to decreased YAP phosphorylation and nuclear translocation. YAP activation promoted increase in nuclear TEA domain family member level, expression of cyclin D1, snail, vimentin, CD44, NS and decrease in E-cadherin levels, thereby inducing stemness and epithelial-mesenchymal-transition (EMT). The Hippo complex with the incorporation of CLDN4 increased stability. Upon low-dose CPE treatment, HT29 cells with BRAFV600E gene mutation showed increased growth, enhanced invasive potential, stemness, and induced EMT phenotype, whereas HCT116 cells, which carry KRASG13D gene mutation, did not show such changes. In an examination of 10 colorectal cancers, an increase in EMT and stemness was observed in CPE (+) and BRAF mutation (+) cases. These findings suggest that C. perfringens might enhance the malignant transformation of SSA/P-D via YAP activation. Our findings further highlight the importance of controlling intestinal flora using probiotics or antibiotics.

Distinct histopathological characteristics in colorectal submucosal invasive carcinoma arising in sessile serrated adenoma/polyp and conventional tubular adenoma

2017 ◽  
Vol 472 (3) ◽  
pp. 383-393 ◽  
Author(s):  
Takashi Murakami ◽  
Hiroyuki Mitomi ◽  
Takashi Yao ◽  
Tsuyoshi Saito ◽  
Tomoyoshi Shibuya ◽  
...  
Keyword(s):  
Invasive Carcinoma ◽  
Tubular Adenoma ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma

scholarly journals Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 434
Author(s):  
Heihachiro Nishimura ◽  
Hirokazu Fukui ◽  
Xuan Wang ◽  
Nobuhiko Ebisutani ◽  
Takashi Nakanishi ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Fusobacterium Nucleatum ◽  
Colorectal Carcinogenesis ◽  
Cell Nuclei ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma ◽  
Reg Iα ◽  
The Relationship

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma 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 β-catenin/REG Iα 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 β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-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 β-catenin nuclear translocation and REG Iα expression.

A Case of Langerhans Cell Histocytosis Masquerading as a Colon Polyp

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S109-S110
Author(s):  
Bradie Bishop ◽  
David Lynch ◽  
Robert Brady
Keyword(s):  
Gastrointestinal Tract ◽  
Systemic Disease ◽  
Langerhans Cell ◽  
Colon Polyp ◽  
Tubular Adenoma ◽  
Hyperplastic Polyps ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma ◽  
Repeat Colonoscopy ◽  
Langerhans Cell Histocytosis

Abstract Langerhans cell histocytosis, otherwise known as eosinophilic granuloma, is a rare neoplastic process composed of Langerhans cells and eosinophils. Most cases present during childhood, with the bones and skin being the most common organs involved. Other organs are occasionally involved, with some systemic cases involving the gastrointestinal tract. Presentations of Langerhans cell histocytosis range from single-organ involvement to systemic involvement. Fewer than five cases of isolated Langerhans cell histocytosis in the gastrointestinal system in adults have been reported. We present a case of Langerhans cell histocytosis incidentally discovered during routine colonoscopy in a 67-year-old otherwise healthy woman. Initial colonoscopy performed 7 years prior demonstrated a sessile serrated adenoma, fragments of tubular adenomas, and hyperplastic polyps. Repeat colonoscopy 3 years later demonstrated a sessile serrated adenoma and hyperplastic polyp. Upon repeat colonoscopy 4 years later, the patient had nine subcentimeter polyps. One of the ascending colon polyp fragments demonstrated a well-circumscribed, submucosal nodule of granular pink histocytes with folded to clefted and reniform nuclei. Numerous eosinophils were present in the background. These findings were consistent with Langerhans cell histocytosis. The remaining polyps were a tubular adenoma and hyperplastic polyps. A CT chest/abdomen/pelvis did not demonstrate any evidence of systemic disease. One year postdiagnosis, the patient had not had recurrence of symptoms. Unifocal Langerhans cell histocytosis rarely presents in the gastrointestinal tract of an adult and is believed to have a good prognosis with limited recurrence. The patient is being closely followed for development of systemic disease.

scholarly journals Mo1739 – Molecular Markers, Mlh1 and Msi Status Differentiate Hyperplastic Polyps from Sessile Serrated Adenoma/Polyps Among African American Patients

2019 ◽  
Vol 156 (6) ◽  
pp. S-828
Author(s):  
Hassan Ashktorab ◽  
Priyanka Kanth ◽  
Nazli Atefi ◽  
Saman Azam ◽  
Babak Shokrani ◽  
...  
Keyword(s):  
African American ◽  
Molecular Markers ◽  
Hyperplastic Polyps ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma

scholarly journals Sessile serrated adenoma invading a diverticulum in the right colon: tips and tricks for a safe complete endoscopic resection

Endoscopy ◽  
2021 ◽  
Author(s):  
Sophie Geyl ◽  
Jérémie Albouys ◽  
Romain Legros ◽  
Hugo Lepetit ◽  
Martin Dahan ◽  
...  
Keyword(s):  
Endoscopic Resection ◽  
Tips And Tricks ◽  
Right Colon ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma ◽  
The Right

scholarly journals Protein C Gene Mutation in an Older Adult Patient with Clostridium perfringens Septicemia-Related Visceral Vein Thrombosis

TH Open ◽  
2021 ◽  
Vol 05 (02) ◽  
pp. e171-e173
Author(s):  
Kiyoko Kanosue ◽  
Satomi Nagaya ◽  
Eriko Morishita ◽  
Masayoshi Yamanishi ◽  
Shinsaku Imashuku
Keyword(s):  
Gene Mutation ◽  
Clostridium Perfringens ◽  
Protein C ◽  
Later Life ◽  
Heterozygous Mutation ◽  
Protein C Deficiency ◽  
Vein Thrombosis ◽  
Thrombosis Risk ◽  
Japanese Male ◽  
Old Japanese

AbstractA 78-year-old Japanese male with Clostridium perfringens septicemia and cholecystitis was found to have thrombosis in the left branch of intrahepatic portal vein as well as superior mesenteric vein. Visceral vein thrombosis (VVT) in this case was associated with protein C deficiency, due to a heterozygous mutation, p. Arg185Met. Our experience emphasizes that VVT, or other thromboembolic events, may occur in later life, triggered by environmental thrombosis risk factors, together with underlying hereditary protein C gene mutation.

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