NOTCH3 limits the epithelial–mesenchymal transition and predicts a favorable clinical outcome in esophageal cancer

Matsuura, Nobuo; Yamasaki, Makoto; Yamashita, Kotaro; Saito, Takuro; Makino, Tomoki; Yamamoto, Keiji; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Eguchi, Hidetoshi; Nakagawa, Hiroshi; Doki, Yuichiro

doi:10.1002/cam4.3933

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…Although the relevance between NOTCH3 variants and prognosis is still unknown, it has been reported that NOTCH3 downregulation decreases chemotherapy sensitivity through activation of epithelial‐mesenchymal transition (EMT), which may lead to worsening prognosis. 36 Considering that numerous mutations in NOTCH family in solid tumors have been reported as loss‐of‐function, 31 , 32 , 33 , 34 we think our result supports these findings.…”

Section: Discussionsupporting

confidence: 82%

Integrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma

Takemoto

Tanimoto²,

Mori

et al. 2021

Cancer Science

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Section: Discussionsupporting

confidence: 82%

Integrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma

Takemoto

Tanimoto²,

Mori

et al. 2021

Cancer Science

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“…The transcription levels of Notch1 were also significantly downregulated in both the cells tested, upon silencing of SNHG6 (Figure 3B). With the implication of Notch3 in the process of EMT as well (Matsuura et al, 2021), we evaluated mRNA levels of Notch3 in cells transfected with SNHG6. As seen in Figure 3C, Notch3 levels were also down albeit not as significantly as those of Notch1.…”

Section: Snhg6 and Emtmentioning

confidence: 99%

Long Non-Coding RNA SNHG6 Supports Glioma Progression Through Upregulation of Notch1, Sox2, and EMT

Nie

Feng

Wang

et al. 2021

Front. Cell Dev. Biol.

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Gliomas, particularly the advanced grade glioblastomas, have poor 5-year survival rates and worse outcomes. lncRNAs and EMT have been extensively studied in gliomas but the disease progression remains poorly understood. SNHG6 has been shown to affect glioma cell proliferation but its effect on EMT of glioma cells along with its effect on disease progression is not known. We screened four glioma cell lines; H4, A172, U87MG, and SW088 and grouped them based on high vs. low SNHG6 expression. Transfections with SNHG6 specific siRNA resulted in induction of apoptosis of high SNHG6 expressing A172 and U87MG cells. This was accompanied by inhibition of EMT and downregulation of EMT-modulating factor Notch1, β-catenin activity and the cancer stem cell marker Sox2. The regulation was not found to be reciprocal as silencing of Notch1 and Sox2 failed to affect SNHG6 levels. The levels of SNHG6 and Notch1 were also found elevated in Grade IV glioma patients (n = 4) relative to Grade II glioma patients (n = 5). These results identify SNHG6 and Notch1 as valid targets for glioma therapy.

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“…Notably, Notch signaling regulates EMT in breast and ovarian cancer, and plays a role in hypoxia-induced EMT in tumor cell lines [ 66 ]. In head and neck squamous cell carcinoma, Notch signaling is similarly implicated in enhancing EMT-mediated cancer plasticity [ 67 ], while in esophageal squamous cell carcinoma, NOTCH3 conversely reduces EMT, with a blockade of Notch promoting expression of mesenchymal markers in esophageal squamous cell carcinoma cell lines [ 68 ]. Collectively, this suggests that Notch signaling can promote or inhibit EMT-mediated cancer plasticity, depending on cellular context.…”

Section: Dysregulated Notch Signaling In Cancermentioning

confidence: 99%

Roles of Notch Signaling in the Tumor Microenvironment

D’Assoro

Leon‐Ferre

Braune

et al. 2022

IJMS

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The Notch signaling pathway is an architecturally simple signaling mechanism, well known for its role in cell fate regulation during organ development and in tissue homeostasis. In keeping with its importance for normal development, dysregulation of Notch signaling is increasingly associated with different types of tumors, and proteins in the Notch signaling pathway can act as oncogenes or tumor suppressors, depending on the cellular context and tumor type. In addition to a role as a driver of tumor initiation and progression in the tumor cells carrying oncogenic mutations, it is an emerging realization that Notch signaling also plays a role in non-mutated cells in the tumor microenvironment. In this review, we discuss how aberrant Notch signaling can affect three types of cells in the tumor stroma—cancer-associated fibroblasts, immune cells and vascular cells—and how this influences their interactions with the tumor cells. Insights into the roles of Notch in cells of the tumor environment and the impact on tumor-stroma interactions will lead to a deeper understanding of Notch signaling in cancer and inspire new strategies for Notch-based tumor therapy.

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NOTCH3 limits the epithelial–mesenchymal transition and predicts a favorable clinical outcome in esophageal cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 36 publications

Integrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma

Integrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma

Long Non-Coding RNA SNHG6 Supports Glioma Progression Through Upregulation of Notch1, Sox2, and EMT

Roles of Notch Signaling in the Tumor Microenvironment

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