Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1

Wang-Bishop, Lihong; Chen, Zheng; Gomaa, Ahmed R.; Lockhart, A. Craig; Salaria, Safia N.; Wang, Jialiang; Lewis, Keeli B.; Ecsedy, Jeffrey; Washington, Kay; Beauchamp, R. Daniel; El–Rifai, Wael

doi:10.1053/j.gastro.2018.10.030

Cited by 70 publications

(56 citation statements)

References 49 publications

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“…The TMAs were used for IHC analysis using ITGBL1 rabbit antibody (17484-1-AP, 1: 200). The composite scoring system 58 which the system integrates the IHC signal intensity and the frequency of positive cells in the cytosol and nucleus. The immunoreactivity for each sample was observed and evaluated by two experienced pathologists.…”

Section: Discussionmentioning

confidence: 99%

Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation

et al. 2020

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Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the premetastatic niche formation and promote metastatic cancer growth by secreting proinflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor-stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.

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Section: Discussionmentioning

confidence: 99%

Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation

et al. 2020

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“… 70 , 71 Abnormal activity of AURKA promotes tumorigenic progression and transformation via defective control at the checkpoint of mitotic spindle. 72 Meanwhile, AURKA is highly expressed in a variety of human cancers, including breast cancer, 73 lung cancer, 74 gastrointestinal cancer, 75 bladder cancer, 76 and oral cancer. 77 A study demonstrated that genetic variations in AURKA might be a reliable predictor of early-stage HCC and a crucial biomarker for HCC development.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma via integrated bioinformatics analysis

Meng

Liu

et al. 2020

J Int Med Res

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Objective The objective was to identify potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Methods Gene expression profile datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HCC and normal samples were identified via an integrated analysis. A protein–protein interaction network was constructed and analyzed using the STRING database and Cytoscape software, and enrichment analyses were carried out through DAVID. Gene Expression Profiling Interactive Analysis and Kaplan–Meier plotter were used to determine expression and prognostic values of hub genes. Results We identified 11 hub genes ( CDK1, CCNB2, CDC20, CCNB1, TOP2A, CCNA2, MELK, PBK, TPX2, KIF20A, and AURKA) that might be closely related to the pathogenesis and prognosis of HCC. Enrichment analyses indicated that the DEGs were significantly enriched in metabolism-associated pathways, and hub genes and module 1 were highly associated with cell cycle pathway. Conclusions In this study, we identified key genes of HCC, which indicated directions for further research into diagnostic and prognostic biomarkers that could facilitate targeted molecular therapy for HCC.

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“…Besides, we discovered that most of these genes have been well studied except TPX2. For example, AURKA promotes tumor proliferation and was associated with worse prognosis in bladder cancer and gastrointestinal cancer [41][42]. Increased AURKB have a poor prognosis in NSCLC [43].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of TPX2-related ceRNA network as prognostic biomarkers in lung adenocarcinoma

Chen¹,

Zhang²,

Li³

et al. 2020

Int. J. Med. Sci.

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Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD (p <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. Conclusions: TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.

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Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1

Abstract: Background & Aims: Activation of KRAS signaling and overexpression of the aurora kinase A (AURKA) are often detected in luminal gastrointestinal cancers. We investigated regulation of

Cited by 70 publications

References 49 publications

Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation

Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation

Identification of potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma via integrated bioinformatics analysis

Comprehensive analysis of TPX2-related ceRNA network as prognostic biomarkers in lung adenocarcinoma

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