NOTCH1 activates the Wnt/β-catenin signaling pathway in colon cancer

Ishiguro, Hideyuki; Okubo, Takeshi; Kuwabara, Yoshiyuki; Kimura, Masahiro; Mitsui, Akira; Sugito, Nobuyoshi; Ogawa, Ryo; Katada, Takeyasu; Tanaka, Tatsuya; Shiozaki, Midori; Mizoguchi, Koji; Samoto, Yosuke; Matsuo, Yoichi; Takahashi, Hiroki; Takiguchi, Shuji

doi:10.18632/oncotarget.19534

Cited by 29 publications

(24 citation statements)

References 53 publications

(58 reference statements)

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“…Some evidence has indicated that cell fate determination and lineage commitment of enterocytes are not governed by a simple rule, but by a complex and multilayered interaction between several pathways [46]. This means that β-catenin is regulated in many ways, for example, NOTCH1 plays a key role in the Wnt pathway, and activation of NOTCH1 is associated with the translocation of β-catenin to the nucleus in colon cancer [47]. Axin expression is positively regulated by β-catenin, and this generates a negative feedback loop that would be expected to decrease cytosolic β-catenin levels [48].…”

Section: Discussionmentioning

confidence: 99%

Plant MIR167e-5p Inhibits Enterocyte Proliferation by Targeting β-Catenin

Chen

et al. 2019

Cells

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MicroRNAs (miRNAs) are important negative regulators of genes involved in physiological and pathological processes in plants and animals. It is worth exploring whether plant miRNAs play a cross-kingdom regulatory role in animals. Herein, we found that plant MIR167e-5p regulates the proliferation of enterocytes in vitro. A porcine jejunum epithelial cell line (IPEC-J2) and a human colon carcinoma cell line (Caco-2) were treated with 0, 10, 20, and 40 pmol of synthetic 2′-O-methylated plant MIR167e-5p, followed by a treatment with 20 pmol of MIR167e-5p for 0, 24, 48, and 72 h. The cells were counted, and IPEC-J2 cell viability was determined by the MTT and EdU assays at different time points. The results showed that MIR167e-5p significantly inhibited the proliferation of enterocytes in a dose- and time-dependent manner. Bioinformatics prediction and a luciferase reporter assay indicated that MIR167e-5p targets β-catenin. In IPEC-J2 and Caco-2 cells, MIR167e-5p suppressed proliferation by downregulating β-catenin mRNA and protein levels. MIR167e-5p relieved this inhibition. Similar results were achieved for the β-catenin downstream target gene c-Myc and the proliferation-associated gene PCNA. This research demonstrates that plant MIR167e-5p can inhibit enterocyte proliferation by targeting the β-catenin pathway. More importantly, plant miRNAs may be a new class of bioactive molecules for epigenetic regulation in humans and animals.

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Section: Discussionmentioning

confidence: 99%

Plant MIR167e-5p Inhibits Enterocyte Proliferation by Targeting β-Catenin

Chen

et al. 2019

Cells

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“…2B). Notch1 functioned as an important role in the Wnt/β-catenin pathway, and the activation of Notch1 was positively related to the nuclear translocation of β-catenin 22 . The accumulation of β-catenin in the nucleus plays an important role in the malignant progression of tumours.…”

Section: Dner Induces Emt In Bc Cellsmentioning

confidence: 99%

DNER promotes epithelial–mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer

Wang

et al. 2020

Cell Death Dis

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Breast cancer (BC) is the most common malignant tumour in women worldwide, and one of the most common fatal tumours in women. Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER) is a transmembrane protein involved in the development of tumours. The role and potential mechanism of DNER in epithelial-mesenchymal transition (EMT) and apoptosis in BC are not fully understood. We find that DNER is overexpressed in BC tissue, especially triple-negative breast cancer (TNBC) tissue, and related to the survival of BC and TNBC patients. In addition, DNER regulates cell EMT to enhance the proliferation and metastasis of BC cells via the Wnt/β-catenin pathway in vitro and in vivo. Moreover, the expression levels of β-catenin and DNER in BD tissue are positively correlated. The simultaneously high expression of DNER and β-catenin contributes to poor prognosis in BC patients. Finally, DNER protects BC cells from epirubicin-induced growth inhibition and apoptosis via the Wnt/ β-catenin pathway. In conclusion, these results suggest that DNER induces EMT and prevents apoptosis by the Wnt/ β-catenin pathway, ultimately promoting the malignant progression of BC. In conclusion, our study demonstrates that DNER functions as an oncogene and potentially valuable therapeutic target for BC.

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“…These studies highlight the importance of NOTCH pathway activation in the maintenance of colon cancer stem cells and in colon cancerogenesis. Interestingly, NOTCH1 was shown to activate the WNT/β-catenin signaling pathway in colon cancer [ 416 ]. In this context, the analysis of primary colon cancer samples showed that the activation of NOTCH1 is associated with the translocation of β-catenin in the nucleus [ 416 ].…”

Section: Colon Cancer Stem Cellsmentioning

confidence: 99%

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

2018

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Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

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NOTCH1 activates the Wnt/β-catenin signaling pathway in colon cancer

Cited by 29 publications

References 53 publications

Plant MIR167e-5p Inhibits Enterocyte Proliferation by Targeting β-Catenin

Plant MIR167e-5p Inhibits Enterocyte Proliferation by Targeting β-Catenin

DNER promotes epithelial–mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

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