Upregulated claudin-1 expression promotes colitis-associated cancer by promoting β-catenin phosphorylation and activation in Notch/p-AKT-dependent manner

Gowrikumar, Saiprasad; Ahmad, Rizwan; Uppada, Srijayaprakash Babu; Washington, Mary Kay; Shi, Chanjuan; Singh, Amar B.; Dhawan, Punita

doi:10.1038/s41388-019-0795-5

Cited by 32 publications

(21 citation statements)

References 37 publications

(62 reference statements)

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“…The upregulated claudin-1 expression can inhibit the goblet cell differentiation and promote colitis-associated cancer in a Notch-dependent manner [ 38 ]. The decreased claudin-1 expression by BLIDF supplementation suggests that BLIDF can alleviate colitis severity in DSS-treated mice [ 39 , 40 ]. The anti-colitis effects of BLIDF were abolished when the gut microbiota was depleted by antibiotics, suggesting that the anti-colitis effects of BLIDF are highly dependent on intestinal microbiota.…”

Section: Discussionmentioning

confidence: 99%

Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota

Tian

et al. 2021

Nutrients

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Supplementation of dietary fiber has been proved to be an effective strategy to prevent and relieve inflammatory bowel disease (IBD) through gut microbiota modulation. However, more attention has been paid to the efficacy of soluble dietary fiber than that of insoluble dietary fiber (IDF). In the present study, we investigated whether IDF from barley leaf (BLIDF) can inhibit gut inflammation via modulating the intestinal microbiota in DSS-induced colitis mice. The mice were fed 1.52% BLIDF-supplemented diet for 28 days. Results demonstrated that feeding BLIDF markedly mitigated DSS-induced acute colitis symptoms and down-regulated IL-6, TNF-α, and IL-1β levels in the colon and serum of colitis mice. BLIDF supplementation effectively reduced the abundance of Akkermansia and increased the abundance of Parasutterella, Erysipelatoclostridium, and Alistipes. Importantly, the anti-colitis effects of BLIDF were abolished when the intestinal microbiota was depleted by antibiotics. Furthermore, the targeted microbiota-derived metabolites analysis suggested that BLIDF feeding can reverse the DSS-induced decline of short-chain fatty acids and secondary bile acids in mice feces. Finally, BLIDF supplementation elevated the expression of occludin and mucin2, and decreased the expression of claudin-1 in colons of DSS-treated mice. Overall, our observations suggest that BLIDF exerts anti-inflammatory effects via modulating the intestinal microbiota composition and increasing the production of microbiota-derived metabolites.

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Section: Discussionmentioning

confidence: 99%

Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota

Tian

et al. 2021

Nutrients

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“…In comparison, the present analysis not only added an additional three studies [ 43 , 44 , 48 ] but also examined the HR for OS and DFS of CRC. We also included all claudin-1 detection methods, including ELISA and RT-PCR, which were excluded in the analysis by Jiang et al In addition, new studies have emerged reporting on claudin-1 and CRC since the previous similar meta-analysis was published in 2017 [ 48 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Claudin-1 Is a Valuable Prognostic Biomarker in Colorectal Cancer: A Meta-Analysis

Zuo

Zhang

Liu

et al. 2020

Gastroenterology Research and Practice

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Background. Claudin-1 plays an important part in maintaining the mucosal structures and physiological functions. Several studies showed a relationship between claudin-1 and colorectal cancer (CRC), but its prognostic significance is inconsistent. This meta-analysis assessed the prognostic value and clinical significance of claudin-1 in CRC. Materials and Methods. We retrieved eligible studies from PubMed, Cochrane Library, Embase, and Web of Science databases before February 10, 2020. The hazard ratio (HR) with 95% confidence interval (CI) was applied to assess the correlation between claudin-1 and prognosis and clinical features. Heterogeneity was assessed by the Cochran Q test and I-square (I2), while publication bias was evaluated by the Begg test and Egger test. Test sequence analysis (TSA) was used to estimate whether the included studies’ number is sufficient. The stability of the results was judged by sensitivity analysis. Metaregression was utilized to explore the possible covariance which may impact on heterogeneity among studies. Results. Eight studies incorporating 1704 patients met the inclusion criteria. Meta-analysis showed that the high expression of claudin-1 was associated with better overall survival (HR, 0.46; 95% CI, 0.28–0.76; P=0.002) and disease-free survival (HR, 0.44; 95% CI, 0.29–0.65; P=0.003) in CRC. In addition, we found that claudin-1 was related to the better tumor type (n=6; RR, 0.60; 95% CI, 0.49–0.73; P<0.00001), negative venous invasion (n=4; RR, 0.81; 95% CI, 0.70–0.95; P=0.001), and negative lymphatic invasion (n=4; RR, 0.83; 95% CI, 0.74–0.92; P=0.0009). Conclusion. The increased claudin-1 expression in CRC is associated with better prognosis. In addition, claudin-1 was related to the better tumor type and the less venous invasion and lymphatic invasion.

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“… 42 In the development of colitis and CAC, macrophages infiltrate the colon and release a series of cytokines to remodel the affected microenvironment and promote the initiation and progression of colon cancer. 43–45 The inhibition of macrophage infiltration or activation induces an efficient antitumor and anti-colitis effect, respectively, in mice and also in clinical use for humans. 43 , 46 , 47 Our study demonstrated that the number of activated macrophages that infiltrated the colons of GDC-0575-treated CAC and colitis mice decreased compared with that of the DMSO-treated control mice; this decrease was accompanied by a reduction in the expression of pro-inflammatory cytokines that were released by the infiltrating macrophages.…”

Section: Discussionmentioning

confidence: 99%

GDC-0575, a CHK1 Inhibitor, Impairs the Development of Colitis and Colitis-Associated Cancer by Inhibiting CCR2+ Macrophage Infiltration in Mice

Li¹,

Huang²,

Li³

et al. 2021

OTT

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Background Checkpoint kinase 1 (CHK1) plays an important role in DNA damage response and cell cycle progression. Thus, targeting CHK1 is an efficient strategy for cancer therapy. Purpose The present study aimed to investigate the potential therapeutic effects of GDC-0575, a CHK1-specific inhibitor, in colitis-associated cancer (CAC) and colitis. Methods We established a DSS-induced acute colitis model and an azoxymethane/dextran sodium sulfate (DSS)-induced CAC model using mice and tested the effect of GDC-0575 on them. Flow cytometry and immunofluorescence were employed to investigate the infiltration of immune cells, and inflammatory cytokine expression in the colon of mice with CAC or colitis was investigated using ELISA and qPCR. We also investigated the correlation between CHK1 and CCL2/CCR2 in human colorectal cancer (CRC) tissues. Results Administration of GDC-0575 significantly inhibited CHK1 expression in the colon and dramatically impaired the development of CAC and colitis in mice. Moreover, the inhibition of CHK1 expression resulted in efficient inhibition of infiltration by iNOS-positive macrophages, but had no significant effect on CD4 T cells, CD8 T cells, and myeloid-derived suppressor cells (MDSCs). Significant downregulation of TNF-α, IL-6, and IL-1β and dramatic upregulation of IL-10 were observed in the colons of both mice with CAC and colitis treated with GDC-0575. CCL2 expression was also downregulated by GDC-0575 in both mice with CAC and colitis; this was followed by the inhibition of CCR2 + macrophage infiltration in the colon. Furthermore, we report a positive correlation between CHK1 expression and CCL2/CCR2 expression in the malignant tissues of patients with CRC. Conclusion Taken together, we infer that GDC-0575 impairs the development of CAC and colitis by regulating cytokine expression and inhibiting CCR2 + macrophage infiltration in mice colon.

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Upregulated claudin-1 expression promotes colitis-associated cancer by promoting β-catenin phosphorylation and activation in Notch/p-AKT-dependent manner

Cited by 32 publications

References 37 publications

Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota

Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota

Claudin-1 Is a Valuable Prognostic Biomarker in Colorectal Cancer: A Meta-Analysis

GDC-0575, a CHK1 Inhibitor, Impairs the Development of Colitis and Colitis-Associated Cancer by Inhibiting CCR2+ Macrophage Infiltration in Mice

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