Claudin‐2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription

Wei, Mingtian; Zhang, Yaguang; Yang, Xuyang; Ma, Pingfan; Li, Yan; Wu, Yangping; Chen, Xiangzheng; Deng, Xiangbing; Yang, Tinghan; Mao, Xiaobing; Qiu, Lei; Wei, Meng; Zhang, Bo; Wang, Ziqiang; Han, Junhong

doi:10.1002/ctm2.667

Cited by 31 publications

(24 citation statements)

References 49 publications

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“…In colorectal cancer, NDRG1 inhibits EMT, migration and invasion through the interaction and promotion of caveolin-1 ubiquitylation [31] . Suppression of NDRG1 transcription can promote colorectal cancer growth and metastasis [32] . In breast cancer, NDRG1 expression is also known to be an independent prognostic factor in in ammatory breast cancer, and NDRG1 is widely described as a metastasis suppressor in breast cancer [33] .…”

Section: Discussionmentioning

confidence: 99%

MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

Wang

Zhou

Xie

et al. 2023

Preprint

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Objective Previous studies have indicated that neurotransmitters play important roles in the occurrence and development of gastric cancer. MAOA is an important catecholamine neurotransmitter-degrading enzyme involvedin the degradation of norepinephrine, epinephrine and serotonin. To find a potential therapeutic target for the treatment of gastric cancer, the biological functions of MAOA and the underlying mechanism in gastric cancer need to be explored. Methods The Cancer Genome Atlas(TCGA), Gene Expression Omnibus (GEO) datasets, Kaplan‒Meier (KM) plotter and Oncomine databases were used to identify the differentially expressed genes, which mainly involved the degradation and synthesis enzymes of neurotransmitters in gastric cancer. We also investigated the expression pattern of MAOA in human and mouse tissues and cell lines by immunohistochemistry and Western blottinganalysis. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and a Seahorse experiment were used to identify the molecular mechanism ofcancer cell glycolysis. MAOA expression and patientsurvival were analysed in the Ren Ji cohort, and univariate and multivariate analyses were performed based on the clinicopathological characteristics of the above samples. Results MAOA expression was significantly downregulatedin gastric cancer tissue and associated with poor patient prognosis. Moreover, the expression level of MAOA in gastric cancer tissue had a close negative correlation with theSUXmax valueof PET-CT in patients. MAOA suppressed tumour growth and glycolysis and promoted cancer cell apoptosis. We also show that MAOA can interact with NDRG1 and regulate glycolysis through suppression of the PI3K/Akt/mTOR pathway. MAOA expression may serve as an independent prognostic factor in gastric cancer patients. Conclusions MAOA attenuated glycolysis and inhibitedthe progression of gastric cancer through the PI3K/Akt/mTOR pathway. Loss of function or downregulation of MAOA can facilitate gastric cancer progression. Overexpression of MAOA and inhibition of the PI3K/Akt/mTOR pathway may provide a potential method for gastric cancer treatment in clinicaltherapeutic regimens.

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Section: Discussionmentioning

confidence: 99%

MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

Wang

Zhou

Xie

et al. 2023

Preprint

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“…These pathways regulate various aspects of the immune response, infection, tumorigenesis, progression, and metastasis in CRC ( 53 – 58 ). High expression of PROM1 , LEMD1 , CLDN2 , PIGR and LCN2 ( Figure 7B ) were associated with CRC cell migration ( 59 , 60 ), promoting colorectal cancer growth and metastasis ( 61 – 63 ). This could explain the poor prognosis of CRC patients with high DDRscore.…”

Section: Discussionmentioning

confidence: 99%

Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma

Wei

Su²,

Zhang³

et al. 2023

Front. Oncol.

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BackgroundColorectal cancer (CRC) is the third most prevalent malignancy and the one of most lethal cancer. Metastatic CRC (mCRC) is the third most common cause of cancer deaths worldwide. DNA damage response (DDR) genes are closely associated with the tumorigenesis and development of CRC. In this study, we aimed to construct a DDR-related gene signature for predicting the prognosis of mCRC patients.MethodsThe gene expression and corresponding clinical information data of CRC/mCRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed for patients between the high-DDRscore and low-DDRscore groups.ResultsWe constructed a prognostic model consisting of four DDR-related genes (EME2, MSH4, MLH3, and SPO11). Survival analysis showed that patients in the high-DDRscore group had a significantly worse OS than those in the low-DDRscore group. The area under the curve (AUC) value of the ROC curve of the predictive model is 0.763 in the training cohort GSE72970, 0.659 in the stage III/IV colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) data portal, and 0.639 in another validation cohort GSE39582, respectively. GSEA functional analysis revealed that the most significantly enriched pathways focused on nucleotide excision repair, base excision repair, homologous recombination, cytokine receptor interaction, chemokine signal pathway, cell adhesion molecules cams, ECM-receptor interaction, and focal adhesion.ConclusionThe DDRscore was identified as an independent prognostic and therapy response predictor, and the DDR-related genes may be potential diagnosis or prognosis biomarkers for mCRC patients.

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Section: Discussionmentioning

confidence: 99%

MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

et al. 2023

View full text Add to dashboard Cite

ObjectivePrevious studies have indicated that neurotransmitters play important roles in the occurrence and development of gastric cancer. MAOA is an important catecholamine neurotransmitter-degrading enzyme involvedin the degradation of norepinephrine, epinephrine and serotonin. To nd a potential therapeutic target for the treatment of gastric cancer, the biological functions of MAOA and the underlying mechanism in gastric cancer need to be explored. MethodsThe Cancer Genome Atlas(TCGA), Gene Expression Omnibus (GEO) datasets, Kaplan-Meier (KM) plotter and Oncomine databases were used to identify the differentially expressed genes, which mainly involved the degradation and synthesis enzymes of neurotransmitters in gastric cancer. We also investigated the expression pattern of MAOA in human and mouse tissues and cell lines by immunohistochemistry and Western blottinganalysis. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and a Seahorse experiment were used to identify the molecular mechanism ofcancer cell glycolysis. MAOA expression and patientsurvival were analysed in the Ren Ji cohort, and univariate and multivariate analyses were performed based on the clinicopathological characteristics of the above samples. ResultsMAOA expression was signi cantly downregulatedin gastric cancer tissue and associated with poor patient prognosis. Moreover, the expression level of MAOA in gastric cancer tissue had a close negative correlation with theSUXmax valueof PET-CT in patients. MAOA suppressed tumour growth and glycolysis and promoted cancer cell apoptosis. We also show that MAOA can interact with NDRG1 and regulate glycolysis through suppression of the PI3K/Akt/mTOR pathway. MAOA expression may serve as an independent prognostic factor in gastric cancer patients. ConclusionsMAOA attenuated glycolysis and inhibitedthe progression of gastric cancer through the PI3K/Akt/mTOR pathway. Loss of function or downregulation of MAOA can facilitate gastric cancer progression. Overexpression of MAOA and inhibition of the PI3K/Akt/mTOR pathway may provide a potential method for gastric cancer treatment in clinicaltherapeutic regimens.

show abstract

Claudin‐2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription

Cited by 31 publications

References 49 publications

MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma

MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

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