EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling

Jia, Liqing; Ge, Xiaolu; Du, Chao; Chen, Linna; Zhou, Yanhong; Xiong, Wei; Xiang, Juanjuan; Li, Guiyuan; Xiao, Guohong; Li, Fang; Li, Zheng

doi:10.1038/s41416-020-01250-4

Cited by 36 publications

(25 citation statements)

References 55 publications

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“…HSP90AB1 is a molecular chaperone with roles in tumorigenesis ( 63 ) that activates the Wnt/β-catenin signaling pathway in gastric cancer ( 64 ) that also enhances the TGF-β/SMAD signaling in lung adenocarcinoma (LUAD) ( 65 ), promoting EMT in both scenarios. In addition, silencing of p53 leads to increased expression of Hsp90 and of its cochaperone activator of heat shock 90 kDa protein ATPase homolog (Aha1) ( 66 ) whose down-regulation leads to rescue of mutant CFTR to the PM ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial–mesenchymal transition

et al. 2022

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Mutations in the CFTR anion channel cause cystic fibrosis (CF) and have also been related to higher cancer incidence. Previously we proposed that this is linked to an emerging role of functional CFTR in protecting against epithelial–mesenchymal transition (EMT). However, the pathways bridging dysfunctional CFTR to EMT remain elusive. Here, we applied systems biology to address this question. Our data show that YAP1 is aberrantly active in the presence of mutant CFTR, interacting with F508del, but not with wt-CFTR, and that YAP1 knockdown rescues F508del-CFTR processing and function. Subsequent analysis of YAP1 interactors and roles in cells expressing either wt- or F508del-CFTR reveal that YAP1 is an important mediator of the fibrotic/EMT processes in CF. Alongside, five main pathways emerge here as key in linking mutant CFTR to EMT, namely, (1) the Hippo pathway; (2) the Wnt pathway; (3) the TGFβ pathway; (4) the p53 pathway; and (5) MYC signaling. Several potential hub proteins which mediate the crosstalk among these pathways were also identified, appearing as potential therapeutic targets for both CF and cancer.

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Section: Discussionmentioning

confidence: 99%

Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial–mesenchymal transition

et al. 2022

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“…As a stress protein, HSP90AB1 is a member of the heat shock protein family [ 26 , 41 ]. It is also closely related to many physiological functions of cells [ 28 , 42 ]. Previous studies have confirmed that HSP90AB1 is closely related to T cell activity [ 25 ], and other studies have confirmed that HSP90AB1 can regulate the expression of Akt [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…The results of proteomic analysis showed that CAP significantly reduced HSP90AB1 and SMARCC1 expression. HSP90AB1, which is one of the HSP90 subtypes, has a critical role in tumorigenesis and progression and is also closely related to T cell activity [ 25 – 28 ]. SMARCC1, which is a member of the SWI/SNF DNA chromatin remodeling complex family, is also associated with tumor progression and T cell activity [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Capecitabine Regulates HSP90AB1 Expression and Induces Apoptosis via Akt/SMARCC1/AP-1/ROS Axis in T Cells

Zhang

Fan

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Transplant oncology is a newly emerging discipline integrating oncology, transplant medicine, and surgery and has brought malignancy treatment into a new era via transplantation. In this context, obtaining a drug with both immunosuppressive and antitumor effects can take into account the dual needs of preventing both transplant rejection and tumor recurrence in liver transplantation patients with malignancies. Capecitabine (CAP), a classic antitumor drug, has been shown to induce reactive oxygen species (ROS) production and apoptosis in tumor cells. Meanwhile, we have demonstrated that CAP can induce ROS production and apoptosis in T cells to exert immunosuppressive effects, but its underlying molecular mechanism is still unclear. In this study, metronomic doses of CAP were administered to normal mice by gavage, and the spleen was selected for quantitative proteomic and phosphoproteomic analysis. The results showed that CAP significantly reduced the expression of HSP90AB1 and SMARCC1 in the spleen. It was subsequently confirmed that CAP also significantly reduced the expression of HSP90AB1 and SMARCC1 and increased ROS and apoptosis levels in T cells. The results of in vitro experiments showed that HSP90AB1 knockdown resulted in a significant decrease in p-Akt, SMARCC1, p-c-Fos, and p-c-Jun expression levels and a significant increase in ROS and apoptosis levels. HSP90AB1 overexpression significantly inhibited CAP-induced T cell apoptosis by increasing the p-Akt, SMARCC1, p-c-Fos, and p-c-Jun expression levels and reducing the ROS level. In conclusion, HSP90AB1 is a key target of CAP-induced T cell apoptosis via Akt/SMARCC1/AP-1/ROS axis, which provides a novel understanding of CAP-induced T cell apoptosis and lays the experimental foundation for further exploring CAP as an immunosuppressant with antitumor effects to optimize the medication regimen for transplantation patients.

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“…We speculated that LUAD patients with high risks may promote the progression of LUAD through the activation of the following pathways, leading to poor prognosis: cell cycle, P53 signaling, DNA replication, adhesion junctions, actin cytoskeleton regulation, cancer pathways, and TGF signaling. P53 [ 27 ], TGF-β [ 28 ] and RHPN2 [ 29 ] participate in LUAD occurrence and development.…”

Section: Discussionmentioning

confidence: 99%

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

Chen

Shen²,

et al. 2021

Aging

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The tumor immune microenvironment of lung cancer is associated with prognosis and immunotherapy efficacy. Long noncoding RNAs are identified as prognostic biomarkers associated with immune functions. We constructed a signature comprising differentially expressed immune-related lncRNAs to predict the prognosis of patients with lung adenocarcinoma. We established the immune-related lncRNA signature by pairing immune-related lncRNAs regardless of expression level and lung adenocarcinoma patients were divided into high- and low-risk groups. The prognosis of patients in the two groups was significantly different; The immune-related lncRNA signature could serve as an independent lung adenocarcinoma prognostic indicator. The signature correlated negatively with B cell, CD4+ T cell, M2 macrophage, neutrophil, and monocyte immune infiltration. Patients with low risk scores had a higher abundance of immune cells and stromal cells around the tumor. Gene set enrichment analysis showed that samples from low-risk group were more active in the IgA production in intestinal immune network and the T and B cell receptor signaling pathway. High-risk groups had significant involvement of the cell cycle, DNA replication, adherens junction, actin cytoskeleton regulation, pathways in cancer, and TGF-β signaling pathways. High risk scores correlated significantly negatively with high CTLA-4 and HAVCR2 expression and higher median inhibitory concentration of common anti-tumor chemotherapeutics (e.g., cisplatin, paclitaxel, gemcitabine) and targeted therapy (e.g., erlotinib and gefitinib). We identified a reliable immune-related lncRNA lung adenocarcinoma prognosis model, and the immune-related lncRNA signature showed promising clinical prediction value.

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EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling

Cited by 36 publications

References 55 publications

Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial–mesenchymal transition

Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial–mesenchymal transition

Capecitabine Regulates HSP90AB1 Expression and Induces Apoptosis via Akt/SMARCC1/AP-1/ROS Axis in T Cells

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

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