Dependence and Guidance Receptors—DCC and Neogenin—In Partial EMT and the Actions of Serine Proteases

Stone, T.W.

doi:10.3389/fonc.2020.00094

Cited by 10 publications

(5 citation statements)

References 122 publications

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“…During this process, epithelial cells are transformed into mesenchymal ones that have high migratory and metastatic capabilities. In this way, E-cadherin as an epithelial protein undergoes downregulation, while an increase occurs in mesenchymal markers such as N-cadherin and vimentin [138][139][140][141]. Consequently, targeting this mechanism remarkably reduces the invasion of cancer cells.…”

Section: Head and Neck Cancersmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-β, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.

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Section: Head and Neck Cancersmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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“…Thus, the molecules who are closely related to EMT could be core biomarkers for early metastasis detection and novel targets for dedicated drug development. As an axon-guidance receptor, NEO1 influenced the direction and rate of cell motility and the direction and size of cell outgrowths such as lammellipodia, a key process of EMT [43]. It was validated that NEO1 absence in Caco-2 CRC cells could induce EMT by increasing Fibronectin 1 expression [29].…”

Section: Discussionmentioning

confidence: 92%

Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer

et al. 2020

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Background Due to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC. Methods Online databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC. Results Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis. Conclusion A tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients.

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“…They are also included in the group of 'subtilase' enzymes in view of the similarity of their substrate selectivity with that of the bacterial serine protease subtilisin. Indeed, subtilisin itself was examined partly for that reason and partly as it has already been shown to have carcinogenic potential by depleting cells of the tumor suppressors Deleted in Colorectal Cancer (DCC), neogenin and uncoordinated-5 [69][70][71]. Subtilisin proved to be as effective as mammalian PSA and CD26 [68].…”

Section: Ido Modulation and Cancer Susceptibilitymentioning

confidence: 99%

Interactions of IDO and the Kynurenine Pathway with Cell Transduction Systems and Metabolism at the Inflammation–Cancer Interface

Stone

Williams

2023

Cancers

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The mechanisms underlying a relationship between inflammation and cancer are unclear, but much emphasis has been placed on the role of tryptophan metabolism to kynurenine and downstream metabolites, as these make a substantial contribution to the regulation of immune tolerance and susceptibility to cancer. The proposed link is supported by the induction of tryptophan metabolism by indoleamine-2,3-dioxygenase (IDO) or tryptophan-2,3-dioxygenase (TDO), in response to injury, infection or stress. This review will summarize the kynurenine pathway and will then focus on the bi-directional interactions with other transduction pathways and cancer-related factors. The kynurenine pathway can interact with and modify activity in many other transduction systems, potentially generating an extended web of effects other than the direct effects of kynurenine and its metabolites. Conversely, the pharmacological targeting of those other systems could greatly enhance the efficacy of changes in the kynurenine pathway. Indeed, manipulating those interacting pathways could affect inflammatory status and tumor development indirectly via the kynurenine pathway, while pharmacological modulation of the kynurenine pathway could indirectly influence anti-cancer protection. While current efforts are progressing to account for the failure of selective IDO1 inhibitors to inhibit tumor growth and to devise means of circumventing the issue, it is clear that there are wider factors involving the relationship between kynurenines and cancer that merit detailed consideration as alternative drug targets.

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Dependence and Guidance Receptors—DCC and Neogenin—In Partial EMT and the Actions of Serine Proteases

Cited by 10 publications

References 122 publications

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer

Interactions of IDO and the Kynurenine Pathway with Cell Transduction Systems and Metabolism at the Inflammation–Cancer Interface

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