Numb has distinct function in lung adenocarcinoma and squamous cell carcinoma

Kikuchi, Hajime; Sakakibara‐Konishi, Jun; Furuta, Megumi; Kikuchi, Eiki; Kikuchi, Junko; Oizumi, Satoshi; Hida, Kyoko; Kaga, Kichizo; Kinoshita, Ichiro; Dosaka‐Akita, Hirotoshi; Nishimura, Masaharu

doi:10.18632/oncotarget.25585

Cited by 13 publications

(14 citation statements)

References 37 publications

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“…With respect to the Numb family, Kikuchi et al demonstrated that NUMB has the opposite role in both types of NSCLC. In LUAD, specifically, this leads to inhibition of tumor proliferation, migration and invasion, whereas in LUSC, it activates these processes [114]. Contrary to this, our OS analysis showed that both LUAD and LUSC have common trends, wherein lower expression of NUMB is favored (Table 3).…”

Section: Signaling Of the Core Components-modulatorscontrasting

confidence: 60%

Notch Signaling Pathway in Cancer—Review with Bioinformatic Analysis

Anusewicz

Orzechowska

2021

Cancers

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Notch signaling is an evolutionarily conserved pathway regulating normal embryonic development and homeostasis in a wide variety of tissues. It is also critically involved in carcinogenesis, as well as cancer progression. Activation of the Notch pathway members can be either oncogenic or suppressive, depending on tissue context. The present study is a comprehensive overview, extended with a bioinformatics analysis of TCGA cohorts, including breast, bladder, cervical, colon, kidney, lung, ovary, prostate and rectum carcinomas. We performed global expression profiling of the Notch pathway core components and downstream targets. For this purpose, we implemented the Uniform Manifold Approximation and Projection algorithm to reduce the dimensions. Furthermore, we determined the optimal cutpoint using Evaluate Cutpoint software to established disease-free and overall survival with respect to particular Notch members. Our results demonstrated separation between tumors and their corresponding normal tissue, as well as between tumors in general. The differentiation of the Notch pathway, at its various stages, in terms of expression and survival resulted in distinct profiles of biological processes such as proliferation, adhesion, apoptosis and epithelial to mesenchymal transition. In conclusion, whether oncogenic or suppressive, Notch signaling is proven to be associated with various types of malignancies, and thus may be of interest as a potential therapeutic target.

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Section: Signaling Of the Core Components-modulatorscontrasting

confidence: 60%

Notch Signaling Pathway in Cancer—Review with Bioinformatic Analysis

Anusewicz

Orzechowska

2021

Cancers

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“…However, the same gene may play different or even contrary roles in different lung cancer subtypes. For instance, in lung adenocarcinoma, Numb protein impairs tumor growth and inhibits the Notch pathway and epithelialmesenchymal transition, whereas in lung squamous cell carcinoma, it may promote proliferation (25). In addition, we noticed that some mutant genes significantly influenced the metastasis/recurrence outcomes, especially ATM.…”

Section: Discussionmentioning

confidence: 88%

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing

Zhang¹,

Wang²,

Ma³

et al. 2021

J Thorac Dis

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This study aimed to use a panel targeting 197 genes and 38 fusions to observe the features of gene variations in lung cancer patients, as well as their prognostic values. Methods:Patients admitted to our hospital between 2016 and 2017 were enrolled. All patients received OseqTM-Drug genetic testing using peripheral venous blood, followed by 1-2 years of observation. Results:For all included patients, 32 genes were observed with mutations. EGFR exhibited the highest mutation rate (46.5%), followed by TP53. The majority of patients carried only one mutant gene. Interestingly, 18 (41.8%) patients showed no mutations, and some cases carried mutations in six genes simultaneously. There was no statistical relationship between mutations and demographic influence.Pathological subtypes were associated with mutations including FLI1, IGF1R, and NOTCH1. A significant correlation was observed between mutant genes and stage at diagnosis, however this requires further confirmation as there was only one case in these mutations: AKT2, AR, STK11, VEGFA, HDAC6, and ASPSCR. For the 33 patients with lymph node metastases at the time of diagnosis, no correlation with any gene mutant was found. Finally, no associations between the survival or prognosis indices (1-year survival, 1-year progression, progression free survival (PFS), and overall survival (OS)) were observed with gene mutations. Conclusions:Together, individualized genetic testing is a feasible and minimally invasive approach in cancer genetic analysis. However, gene mutation detection has a limited efficacy in the prediction of prognosis.

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“…However, Numb may have promoter function in some cancers and a suppressor function in others. For example, Numb overexpression inhibits tumor growth and the epithelial-mesenchymal transition in prostate carcinoma, esophageal squamous cell carcinoma, adenocarcinoma of the lung, and breast cancer[ 43 , 44 ], but it promotes cell proliferation in hepatocellular carcinoma and squamous cell carcinoma of the lung[ 45 ]. Therefore, the influence of Numb in oncogenesis might be related to the type of malignancy or the histological subtype.…”

Section: Discussionmentioning

confidence: 99%

“…The present study revealed that Numb expression is higher in well-differentiated tumors, at earlier stages, and in patients without lymph node metastases, in contrast to the findings for Notch-1. Numerous experimental studies have shown that Numb protein expression is associated with cell differentiation in both normal tissues and tumors, concluding that it is a determinant of cell fate[ 41 - 44 ]. Similar findings have been obtained in experimental studies involving CRC cell culture.…”

Section: Discussionmentioning

confidence: 99%

Expression of Notch pathway components (Numb, Itch, and Siah-1) in colorectal tumors: A clinicopathological study

Gonulcu

Ünal

Başsorgun

et al. 2020

WJG

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BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs, including the colon. Accordingly, studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression. Although Numb, Itch, and seven in absentia homolog-1 (Siah-1) have been shown to contribute to the regulation of Notch signaling, their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date. AIM To evaluate Numb, Itch, and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior. METHODS Expression of Notch-1, Numb, Itch, and Siah-1 was investigated in 50 colorectal carcinomas, 30 adenomas, and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analyses. RESULTS In contrast to Notch-1, which is expressed at higher levels in tumor tissues and adenomas, expression of Numb, Itch, and Siah-1 was stronger and more frequent in normal mucosa ( P < 0.01). There was a positive correlation between Notch-1 expression and high histological grade, the presence of lymph node metastasis, and advanced-stage tumors, whereas expression of Numb, Itch, and Siah-1 was absent or reduced in tumors with these clinicopathological parameters ( P < 0.05). In survival analysis, expression of Notch was related to poor prognosis but that of Numb, Itch, and Siah-1 correlated with improved survival ( P < 0.05). Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis ( P < 0.05). CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb, Itch, and Siah-1 expression is associated with carcinogenesis. Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma (CRC) progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.

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Numb has distinct function in lung adenocarcinoma and squamous cell carcinoma

Cited by 13 publications

References 37 publications

Notch Signaling Pathway in Cancer—Review with Bioinformatic Analysis

Notch Signaling Pathway in Cancer—Review with Bioinformatic Analysis

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing

Expression of Notch pathway components (Numb, Itch, and Siah-1) in colorectal tumors: A clinicopathological study

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