Notch Pathway: A Journey from Notching Phenotypes to Cancer Immunotherapy

Monticone, Giulia; Miele, Lucio

doi:10.1007/978-3-030-55031-8_13

Cited by 17 publications

(18 citation statements)

References 163 publications

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“…Notch signaling is a highly conserved signaling pathway that mediates the interaction between neighboring cells, and is widely found in various organisms (18). Studies have shown that the activation of the Notch signaling pathway plays a vital role in cell proliferation, differentiation and apoptosis (19)(20)(21). Recent findings have highlighted the role of the Notch signaling pathway in the development of a variety of human cancers, including BC, melanoma, ovarian cancer, and PRAD (22,23).…”

Section: Discussionmentioning

confidence: 99%

Myelin and lymphocyte protein 2 regulates cell proliferation and metastasis through the Notch pathway in prostate adenocarcinoma

Zheng¹,

Wang²,

Zhang³

et al. 2021

Transl Androl Urol

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Background: Myelin and lymphocyte protein 2 (MAL2) is a proven oncogene in some human tumors. However, currently, little is known about the function of MAL2 in prostate adenocarcinoma (PRAD). This study sought to investigate the role of MAL2 on PRAD progression.Methods: MAL2 expression in PRAD was first analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA) database. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay and Western blot assay were used to detect the expression of MAL2 in PRAD tissues and cell lines.Additionally, immunohistochemistry (IHC) straining was used to detect the expression of MAL2 in PRAD pathological tissues. The Cell Counting Kit-8 (CCK-8) assay, clone formation assay and Flow cytometry were performed to investigate the effect of MAL2 on PRAD cell proliferation and cell apoptosis. Cell migration and invasion were measured by Transwell assay. The effect of MAL2 on epithelial-mesenchymal transition (EMT) progression and the Notch signaling pathway in PRAD was also investigated.Results: MAL2 was discovered to be obviously upregulated in PRAD tissues and cell lines. The upregulation of MAL2 was closely associated with tumor, nodes and metastases (TNM) stage, the Gleason score and metastasis of PRAD patients, and affected the prognosis of PRAD patients. Functionally, the depletion of MAL2 suppressed cell proliferation, migration, invasion, and EMT progression, and promoted cell apoptosis of PRAD cells. In an in vivo experiment, MAL2 knockdown significantly suppressed tumor growth in mice. Further, inhibiting the Notch pathway reversed the effect of MAL2 knockdown on PRAD progression.

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Section: Discussionmentioning

confidence: 99%

Myelin and lymphocyte protein 2 regulates cell proliferation and metastasis through the Notch pathway in prostate adenocarcinoma

Zheng¹,

Wang²,

Zhang³

et al. 2021

Transl Androl Urol

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“…NOTCH pathway has 4 receptors and 5 ligands. 11 When a ligand combines with a NOTCH receptor, the γ-secretase complex liberates the NOTCH intracellular domain (NICD), and then transfers to the nucleus, leading to the transcriptional activation of NOTCH target genes such as HES and HEY. 12 In cutaneous malignant melanoma, activation of the NOTCH pathway is linked to the development of this disease.…”

Section: Introductionmentioning

confidence: 99%

“…The NOTCH pathway is a crucial regulator in many aspects of cancer biology. NOTCH pathway has 4 receptors and 5 ligands 11 . When a ligand combines with a NOTCH receptor, the γ‐secretase complex liberates the NOTCH intracellular domain (NICD), and then transfers to the nucleus, leading to the transcriptional activation of NOTCH target genes such as HES and HEY 12 .…”

Section: Introductionmentioning

confidence: 99%

ZFPM2‐AS1 facilitates cell proliferation and migration in cutaneous malignant melanoma through modulating miR‐650/NOTCH1 signaling

Liu

et al. 2021

Dermatologic Therapy

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Aberrant expression of long non-coding RNA (lncRNA) zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) has been identified in many tumors, but its role in cutaneous malignant melanoma remains largely obscure. Our present study was intended to unveil the role and potential mechanism of ZFPM2-AS1 in cutaneous malignant melanoma. RT-qPCR was utilized to analyze ZFPM2-AS1 expression in cutaneous malignant melanoma cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell analyses were utilized to assess ZFPM2-AS1 function on cell proliferation, apoptosis, and migration. Luciferase reporter, RNA immunoprecipitation, and RNA-pull down assays were applied to probe the regulatory mechanism of ZFPM2-AS1 in cutaneous malignant melanoma cells. Up-regulation of ZFPM2-AS1 was discovered in cutaneous malignant melanoma cells. ZFPM2-AS1 deletion restrained cell proliferation, migration, and elevated cell apoptosis in cutaneous malignant melanoma. ZFPM2-AS1 regulated notch receptor 1 (NOTCH1) to activate the NOTCH pathway. ZFPM2-AS1 acted as a competing endogenous RNA (ceRNA) to affect NOTCH1 expression via sponging miR-650. Collectively, ZFPM2-AS1 exerted an oncogenic role in cutaneous malignant melanoma progression via targeting miR-650/NOTCH1 signaling. Our study might offer a novel sight for cutaneous malignant melanoma treatment.

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“…The Notch signalling pathway is highly conserved and plays key roles in many aspects of development and homeostasis (Bray, 2016). Aberrant Notch signalling results in a number of inherited diseases and is associated with various cancers and other acquired disorders (Mašek & Andersson, 2017; Nowell & Radtke, 2017; Siebel & Lendahl, 2017; Monticone & Miele, 2021). As both the Notch receptors and the ligands are single‐pass type I transmembrane proteins, signalling is initiated by direct protein–protein contact between adjacent cells, which may occur in some instances via long cell processes such as cytonemes (Boukhatmi et al , 2020; Cohen et al , 2010; Hunter et al , 2019; De Joussineau et al , 2003; Huang & Kornberg, 2015).…”

Section: Introductionmentioning

confidence: 99%

Delta C2 Domain β1-2 loop contributes to robust Notch signalling

Martins

Meng

Korona

et al. 2021

Preprint

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Accurate Notch signalling is critical for organism development and homeostasis. Fine-tuning of Notch-ligand interactions have substantial impact on signalling-outputs. Recent structural studies identified a conserved N-terminal C2 domain in human Notch ligands which conferred phospholipid binding in vitro. Here we show that Drosophila ligands adopt the same C2 domain structure with analogous variations in the loop regions, including the so-called β1-2 loop that has been associated with phospholipid binding. Mutations in the β1-2 loop of Delta C2 domain retain Notch binding but have impaired ability to interact with phospholipids in vitro. To investigate its role in vivo we deleted five residues within the β1-2 loop of endogenous Delta by CRISPR/Cas9 gene editing. Strikingly, this change compromised ligand function. The modified Delta enhanced phenotypes produced by Delta loss of function alleles and suppressed that of Notch alleles. As the modified protein was present on the cell surface in normal amounts, these results argue that C2 domain phospholipid-binding is necessary for robust signalling in vivo where the balance of cis and trans ligand-receptor interactions is finely tuned.

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Notch Pathway: A Journey from Notching Phenotypes to Cancer Immunotherapy

Cited by 17 publications

References 163 publications

Myelin and lymphocyte protein 2 regulates cell proliferation and metastasis through the Notch pathway in prostate adenocarcinoma

Myelin and lymphocyte protein 2 regulates cell proliferation and metastasis through the Notch pathway in prostate adenocarcinoma

ZFPM2‐AS1 facilitates cell proliferation and migration in cutaneous malignant melanoma through modulating miR‐650/NOTCH1 signaling

Delta C2 Domain β1-2 loop contributes to robust Notch signalling

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