Systematic expression analysis of the CELSR family reveals the importance of CELSR3 in human lung adenocarcinoma

Li, Yishuai; Zhu, Longyu; Hao, Ran; Li, Yuejun; Zhao, Qinghao; Li, Shujun

doi:10.1111/jcmm.16497

Cited by 8 publications

(6 citation statements)

References 48 publications

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“…Flamingo is required for tumorigenesis in Drosophila Ras V12 tumors Planar polarity has been linked to tumorigenesis in several organisms, tumor models, and patient tumor samples (Kaucká et al, 2013;Asad et al, 2014;Puvirajesinghe et al, 2016;VanderVorst et al, 2018;Chen et al, 2021c;Li et al, 2021;Chen et al, 2021b). We explored how the core PCP complex might be involved in tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Evidence is accumulating that a human ortholog of Fmi, CELSR3, is expressed at high levels in a range of solid tumors, including lung, prostate, pancreatic, hepatic, ovarian and colorectal cancers, and in some cases has been shown to be associated with poor prognosis (Katoh and Katoh, 2007;Erkan et al, 2010;Asad et al, 2014;Goryca et al, 2018;Chen et al, 2021a;Li et al, 2021). If CELSR3 is promoting winner cell behavior in these tumors, as might be predicted from its function in Drosophila, this could provide the rationale for future efforts to understand the mechanism by which Fmi/CELSR3 facilitates cell competition, with the goal of identifying an intervention that could blunt or perhaps even eliminate the aggressiveness of an array of highly morbid cancers.…”

Section: Fmi Cell Competition and Cancermentioning

confidence: 99%

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Flamingo participates in multiple models of cell competition

Bosch,

Cho,

Axelrod

2023

Preprint

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The growth and survival of cells with different fitness, such as those with a proliferative advantage or a deleterious mutation, is controlled through cell competition. During development, cell competition enables healthy cells to eliminate less fit cells that could jeopardize tissue integrity, and facilitates the elimination of pre-malignant cells by healthy cells as a surveillance mechanism to prevent oncogenesis. Malignant cells also benefit from cell competition to promote their expansion. Despite its ubiquitous presence, the mechanisms governing cell competition, particularly those common to developmental competition and tumorigenesis, are poorly understood. Here, we show that in Drosophila, the planar cell polarity (PCP) protein Flamingo (Fmi) is required by winners to maintain their status during cell competition in malignant tumors to overtake healthy tissue, in pre-malignant cells as they grow among wildtype cells, in healthy cells to eliminate pre-malignant cells, and by supercompetitors to occupy excessive territory within wildtype tissues. "Would-be" winners that lack Fmi are unable to over-proliferate, and instead become losers. We demonstrate that the role of Fmi in cell competition is independent of PCP, and that it uses a distinct mechanism that may more closely resemble one used in other less well defined functions of Fmi.

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Section: Resultsmentioning

confidence: 99%

Section: Fmi Cell Competition and Cancermentioning

confidence: 99%

Flamingo participates in multiple models of cell competition

Bosch,

Cho,

Axelrod

2023

Preprint

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“…Lung adenocarcinoma (LUAD) is associated with significant morbidity and mortality 13 . There has been an increase in the incidence of lung adenocarcinoma in recent years, and despite using a variety of treatment methods, the mortality rate remains high 14 .…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Niu

Zhao

et al. 2022

Sci Rep

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Lung adenocarcinoma (LUAD) is one of the most universal types of cancer all over the world and its morbidity continues to rise year by year. Growing evidence has demonstrated that endoplasmic reticulum stress is highly activated in cancer cells and plays a key role in regulating the fate of cancer cells. However, the role and mechanism of endoplasmic reticulum stress in lung adenocarcinoma genesis and development remains unclear. In this research, we developed a prognostic model to predict the overall survival of patients with LUAD utilizing endoplasmic reticulum stress-related genes and screened out potential small molecular compounds, which could assist the clinician in making accurate decisions and better treat LUAD patients. Firstly, we downloaded 419 endoplasmic reticulum stress-related genes (ERSRGs) from Molecular Signatures Database (MSigDB). Secondly, we obtained information about the transcriptome profiling and corresponding clinical data of 59 normal samples and 535 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database. Next, we used the DESeq2 package to identify differentially expressed genes related to endoplasmic reticulum stress. We performed univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis to establish a prognostic model for LUAD patients based on ERSRGs. Then, we carried out univariate and multivariate independent prognostic analysis of endoplasmic reticulum stress-related gene (ERSRG) score and some clinical traits of lung adenocarcinoma. Additionally, we developed a clinically applicable nomogram for predicting survival for LUAD patients over one, three, and five years. Moreover, we carried out a drug sensitivity analysis to identify novel small molecule compounds for LUAD treatment. Finally, we examined the tumor microenvironment (TME) and immune cell infiltrating analysis to explore the interactions between immune and cancer cells. 142 differentially expressed ERSRGs were identified by using the DESeq2 package. A prognostic model was built based on 7 differentially expressed ERSRGs after performing univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. According to the results of univariate and multivariate independent prognostic analysis, we found ERSRG score can be used as an independent prognostic maker. Using the Kaplan–Meier curves, we found low-risk patients had higher survival probability than high-risk patients in both training set and test set. A nomogram was drawn to predict 1-, 3-, and 5-year survival probability. The calibration curves explained good performance of the model for the prediction of survival. Phenformin, OSU-03012, GSK-650394 and KIN001-135 were identified as the drugs most likely to provide important information to clinicians about the treatment of LUAD patients. A prognostic prediction model was established based on 7 differentially expressed ERSRGs (PDX1, IGFBP1, DDIT4, PPP1R3G, CFTR, DERL3 and NUPR1), which could effectively predict the prognosis of LUAD patients and give a reference for clinical doctors to help LUAD patients to make better treatment tactics. Based on the 4 small molecule compounds (Phenformin, OSU-03012, GSK-650394 and KIN001-135) we discovered, targeting endoplasmic reticulum stress-related genes may also be a therapeutic approach for LUAD patients.

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“…PAX8 promotes the proliferation of gastric cancer cells ( Bie et al, 2019 ). Low expression of CELSR3 significantly reduces the migration and invasion of lung adenocarcinoma cells ( Li et al, 2021 ). CELSR3 expression may serve as a prognostic biomarker in patients with prostate cancer and may predict poor outcomes ( Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel tumor driver gene signature for diagnosis and prognosis of head and neck squamous cell carcinoma

Liu

Liu²,

Ding³

et al. 2022

Front. Mol. Biosci.

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Objective: Head and neck squamous cell carcinoma (HNSCC) is a common heterogeneous cancer with complex carcinogenic factors. However, the current TNM staging criteria to judge its severity to formulate treatment plans and evaluate the prognosis are particularly weak. Therefore, a robust diagnostic model capable of accurately diagnosing and predicting HNSCC should be established.Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Key prognostic genes associated with HNSCC were screened with the weighted gene co-expression network analysis and least absolute shrinkage and selection operator (LASSO) Cox regression model analysis. We used the timeROC and survival R packages to conduct time-dependent receiver operating characteristic curve analyses and calculated the area under the curve at different time points of model prediction. Patients in the training and validation groups were divided into high- and low-risk subgroups, and Kaplan-Meier (K-M) survival curves were plotted for all subgroups. Subsequently, LASSO and support vector machine algorithms were used to screen genes to construct diagnostic model. Furthermore, we used the Wilcoxon signed-rank test to compare the half-maximal inhibitory concentrations of common chemotherapy drugs among patients in different risk groups. Finally, the expression levels of eight genes were measured using quantitative real-time polymerase chain reaction and immunohistochemistry.Results: Ten genes (SSB, PFKP, NAT10, PCDH9, SHANK2, PAX8, CELSR3, DCLRE1C, MAP2K7, and ODF4) with prognostic potential were identified, and a risk score was derived accordingly. Patients were divided into high- and low-risk groups based on the median risk score. The K-M survival curves confirmed that patients with high scores had significantly worse overall survival. Receiver operating characteristic curves proved that the prognostic signature had good sensitivity and specificity for predicting the prognosis of patients with HNSCC. Univariate and multivariate Cox regression analyses confirmed that the gene signature was an independent prognostic risk factor for HNSCC. Diagnostic model was built by identifying eight genes (SSB, PFKP, NAT10, PCDH9, CELSR3, DCLRE1C, MAP2K7, and ODF4). The high-risk group showed higher sensitivity to various common chemotherapeutic drugs. DCLRE1C expression was higher in normal tissues than in HNSCC tissues.Conclusion: Our study identified the important role of tumor-driver genes in HNSCC and their potential clinical diagnostic and prognostic values to facilitate individualized management of patients with HNSCC.

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Systematic expression analysis of the CELSR family reveals the importance of CELSR3 in human lung adenocarcinoma

Cited by 8 publications

References 48 publications

Flamingo participates in multiple models of cell competition

Flamingo participates in multiple models of cell competition

Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Identification and validation of a novel tumor driver gene signature for diagnosis and prognosis of head and neck squamous cell carcinoma

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