TRIM11 Promotes Proliferation, Migration, Invasion and EMT of Gastric Cancer by Activating β-Catenin Signaling

Lan, Qingzhi; Tan, Xiaoping; He, Pengzhan; Li, Wei; Tian, Shan; Dong, Weiguo

doi:10.2147/ott.s289922

Cited by 23 publications

(24 citation statements)

References 36 publications

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“…In line with these results, our results showed that TRIM11 was elevated in most of the GC cases (56.67%) and associated with poor clinical outcomes. In contrast to their report [22], our study revealed that TRIM11 protein expression was an indicator of lymph node metastasis in GC patients. Moreover, we demonstrated that TRIM11 depletion significantly inhibited cell growth and invasion, whereas these were enhanced upon TRIM11 overexpression.…”

Section: Discussioncontrasting

confidence: 99%

“…Several studies have shown that Axin1 protein expression is frequently regulated by proteasomal degradation and that inhibition of Axin1 results in the activation of the Wnt/ β-catenin pathway [36,37]. Moreover, it has been reported that TRIM11 is involved in the activation of the β-catenin pathway via the ubiquitination and degradation of Axin1 in lymphomas [29] and that it promotes cell growth and epithelial-mesenchymal transition in gastric cancer by activating β-catenin signaling [22]. Here, we demonstrated for the first time that TRIM11 binds to Axin1, thus shortening the half-life of Axin1 and leading to activation of the Wnt/β-catenin pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Signaling pathways underlying dysregulated TRIM11 function include the transduction nodes EGFR, Akt, and p53, which are highly related to oncogenesis [14,[19][20][21]. Recently, it has been demonstrated that TRIM11 is involved in the activation of the β-catenin signaling pathway via the EMT (epithelialmesenchymal transition) process in GC [22]. Nevertheless, the exact correlations between TRIM11 and Wnt/β-catenin signaling in GC still need to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

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The E3 Ubiquitin Ligase TRIM11 Facilitates Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway via Destabilizing Axin1 Protein

Zhou

Wang

Zhong

et al. 2022

Journal of Oncology

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Background. Aberrant expression of tripartite motif 11 (TRIM11) and the Wnt/β-catenin pathway are essential for facilitating tumorigenesis and progression in multiple types of cancer. Aim. To investigate the molecular changes linking the dysregulation of TRIM11 and Wnt/β-catenin pathway activation in gastric cancer (GC) progression. Methods. The expression levels of TRIM11 were detected in GC tissues and cells by immunohistochemistry and western blotting. The role of TRIM11 in the growth, proliferation, and invasion of gastric cancer cells was observed by a series of cell functional experiments and further verified in vivo. Co-immunoprecipitation (Co-IP), immunofluorescence, cycloheximide, and western blotting assays and other experiments were conducted to explore the mechanisms of TRIM11 underlying the regulation of the Wnt/β-catenin pathway. For further verification, rescue experiments were performed by cotransfection of TRIM11 and Axin1 siRNA in GC cells. Results. Using Co-IP assays, we identified TRIM11 as a potent binding partner of Axin1 in GC cells. Elevated TRIM11 levels were significantly correlated with unfavorable clinical outcomes and poor survival in patients with GC. In addition, TRIM11 promoted the cell proliferation and invasion capacities of GC cells in vitro and tumor growth in vivo. Mechanistic investigations revealed that TRIM11 destabilized Axin1 protein by interacting with Axin1, thus inducing the activation of the Wnt/β-catenin pathway. Moreover, we found that the oncogenic effects of TRIM11 on GC cells were partly mediated by suppression of Axin1. Furthermore, the protein expression of TRIM11 and Axin1 was negatively correlated in GC tissues. Conclusion. Collectively, our findings not only establish a pivotal TRIM11-Axin1-β-catenin axis in driving GC progression but also indicate that TRIM11 serves as a valuable therapeutic target for the treatment of GC patients.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The E3 Ubiquitin Ligase TRIM11 Facilitates Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway via Destabilizing Axin1 Protein

Zhou

Wang

Zhong

et al. 2022

Journal of Oncology

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“…TRIM family members have attracted more and more attention because of their important roles in cancer. Increasing evidence indicates that TRIM family proteins act as regulators of oncoproteins or tumor suppressor proteins, thus regulating cell growth, migration, metabolism, autophagy, and other biological processes ( 12 , 54 , 55 ). Their abnormal expressions and potential mechanisms have been confirmed in diverse cancers.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Prognostic Values of the TRIM Family in Hepatocellular Carcinoma

et al. 2021

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BackgroundAccumulating studies have demonstrated the abnormal expressions and prognostic values of certain members of the tripartite motif (TRIM) family in diverse cancers. However, comprehensive prognostic values of the TRIM family in hepatocellular carcinoma (HCC) are yet to be clearly defined.MethodsThe prognostic values of the TRIM family were evaluated by survival analysis and univariate Cox regression analysis based on gene expression data and clinical data of HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression profiles, protein–protein interaction among the TRIM family, prediction of transcription factors (TFs) or miRNAs, genetic alterations, correlations with the hallmarks of cancer and immune infiltrates, and pathway enrichment analysis were explored by multiple public databases. Further, a TRIM family gene-based signature for predicting overall survival (OS) in HCC was built by using the least absolute shrinkage and selection operator (LASSO) regression. TCGA–Liver Hepatocellular Carcinoma (LIHC) cohort was used as the training set, and GSE76427 was used for external validation. Time-dependent receiver operating characteristic (ROC) and survival analysis were used to estimate the signature. Finally, a nomogram combining the TRIM family risk score and clinical parameters was established.ResultsHigh expressions of TRIM family members including TRIM3, TRIM5, MID1, TRIM21, TRIM27, TRIM32, TRIM44, TRIM47, and TRIM72 were significantly associated with HCC patients’ poor OS. A novel TRIM family gene-based signature (including TRIM5, MID1, TRIM21, TRIM32, TRIM44, and TRIM47) was built for OS prediction in HCC. ROC curves suggested the signature’s good performance in OS prediction. HCC patients in the high-risk group had poorer OS than the low-risk patients based on the signature. A nomogram integrating the TRIM family risk score, age, and TNM stage was established. The ROC curves suggested that the signature presented better discrimination than the similar model without the TRIM family risk score.ConclusionOur study identified the potential application values of the TRIM family for outcome prediction in HCC.

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“…Studies have shown that β2-AR is an important effector molecule for chronic stress-mediated adverse effects on tumor progression [8,13,14]. EMT is an important factor affecting tumor invasion and metastasis [15][16][17][18]. In our study, we treated MGC-803 cells with ISO, a nonselective β-adrenergic receptor (βAR) agonist of β2-AR, at different concentrations and found that 20 μM ISO obviously upregulated the expression of β2-AR (Fig.…”

Section: β2-ar Positively Regulates Emt In Human Gastric Cancer Cellsmentioning

confidence: 73%

PlexinA1 activation induced by β2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells

Liu¹,

Hao²,

Zhao³

et al. 2022

J. Cancer

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With the medical model shifting from a single biomedical model to a biopsychological-social model, the impact of psychosocial factors on cancer patients has attracted attention. Studies have shown that chronic stress caused by long-term psychological stress, such as anxiety and depression, can promote the malignant progression of tumors by acting on β2-adrenergic receptor (β2-AR). β2-AR can promote tumor migration by activating epithelial-mesenchymal transition (EMT). However, the underlying mechanisms in the regulation of EMT by β2-AR are still unclear. In this study, we established a chronic stress model by treating MGC-803 and SGC-7901 human gastric cancer cells with isoproterenol (ISO), a β2-AR agonist. EMT in the two gastric cancer cell lines was enhanced after ISO treatment. Thereafter, we found that the interaction between β2-AR and PlexinA1 was involved in the process by which chronic stress affects EMT in both MGC-803 and SGC-7901 cells. Moreover, the activation of β2-AR by ISO increased the expression of PlexinA1, activated JAK-STAT3 signaling and further promoted EMT in human gastric cancer cells. Importantly, the knockdown of PlexinA1 by small hairpin RNAs inhibited JAK-STAT3 signaling and abolished the EMT induced by β2-AR. In conclusion, PlexinA1 was an important downstream target of β2-AR, through which β2-AR promoted EMT in human gastric cancer cells by activating JAK-STAT3 signaling.

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TRIM11 Promotes Proliferation, Migration, Invasion and EMT of Gastric Cancer by Activating β-Catenin Signaling

Cited by 23 publications

References 36 publications

The E3 Ubiquitin Ligase TRIM11 Facilitates Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway via Destabilizing Axin1 Protein

The E3 Ubiquitin Ligase TRIM11 Facilitates Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway via Destabilizing Axin1 Protein

Comprehensive Analysis of the Prognostic Values of the TRIM Family in Hepatocellular Carcinoma

PlexinA1 activation induced by β2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells

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