ALEX1, a novel tumor suppressor gene, inhibits gastric cancer metastasis via the PAR-1/Rho GTPase signaling pathway

Pang, Li; Li, Jianfang; Zang, Mingde; Fan, Zhiyuan; Yu, Beiqin; Xin, Wu; Li, Chen; Yan, Min; Zhu, Zhenggang; Liu, Bingya

doi:10.1007/s00535-017-1329-y

Cited by 21 publications

(18 citation statements)

References 32 publications

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“…Fujimoto et al reported that PAR1 induced GC cells to become stem-like, inhibited yes-associated protein (YAP) phosphorylation, and increased YAP activity via Rho GTPase [42]. Pang et al reported that thrombin-induced RhoA and Rac1 activation could be significantly inhibited by ALEX1 overexpression, which indicated that ALEX1 could inhibit tumor metastasis through the PAR-1/Rho GTPase signaling pathway [43]. The PI3K pathway plays pivotal roles in many essential cellular processes including cell growth, differentiation, invasion, metastasis, and resistance to chemotherapy [5].…”

Section: Topological Analyses Of the Gc Related Lncrna-mrna Networkmentioning

confidence: 99%

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

Wang

Zhao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in gastric cancer (GC) remains unclear. Methods: We reannotated the GC gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global GC triple network. A further clustering and random walk with restart analyses was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine expression of lncRNA RP11-363E7.4. Kaplan-Meier analyses was performed to evaluate the prognostic value of lncRNA RP11-363E7.4. Results: We constructed a gastric cancer lncRNA-miRNA-mRNA network (GCLMN) including six lncRNAs, 332 mRNAs, and 3,707 edges. For the shared lncRNA RP11-363E7.4, the interacting gene and microRNA functional enrichment studies implied that lncRNA RP11-363E7.4 might function as a new regulator in GC. The expression of lncRNA RP11-363E7.4 was downregulated compared with that of paracarcinoma tissues in five GC samples. High expression of lncRNA RP11-363E7.4 was found to be correlated to better overall survival (OS) for GC patients. Conclusions: This study focused on GC lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA RP11-363E7.4 was a new GC risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of GC.

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Section: Topological Analyses Of the Gc Related Lncrna-mrna Networkmentioning

confidence: 99%

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

Wang

Zhao

et al. 2018

Cell Physiol Biochem

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“…Thrombin-activated PAR-1 induces EMT (epithelial-mesenchymal transition, EMT) in gastric cancer cell lines [ 80 ]. Overexpression of NF-κB, EGFR, and TN-C also activated PAR-1 expression, which in turn promoted gastric cancer cell growth and invasion [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer

Liu

Song

et al. 2017

Oncotarget

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PAR-1 is expressed not only in epithelium, neurons, astrocytes, immune cells, but also in cancer-associated fibroblasts, ECs (epithelial cells), myocytes of blood vessels, mast cells, and macrophages in tumor microenvironment, whereas PAR-1 stimulates macrophages to synthesize and secrete thrombin as well as other growth factors, resulting in enhanced cell proliferation, tumor growth and metastasis. Therefore, considerable effort has been devoted to the development of inhibitors targeting PAR-1. Here, we provide a comprehensive review of PAR-1’s role in cancer invasiveness and dissemination, as well as potential therapeutic strategies targeting PAR-1 signaling.

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“…Therefore, targeted GTPase therapy is also being explored. For example, ALEX1 functions in gastric cancer through the PAR-1/Rho GTPase signaling pathway, becoming a new target for tumor inhibition [32]. RhoA-mediated Fbxw7 regulates the apoptosis of tumor cells and other phenotypes in gastric cancer [33].…”

Section: Discussionmentioning

confidence: 99%

Features of alternative splicing in stomach adenocarcinoma and their clinical implication: a research based on massive sequencing data

Zhang

Niu

et al. 2020

BMC Genomics

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Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed. Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events. Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

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ALEX1, a novel tumor suppressor gene, inhibits gastric cancer metastasis via the PAR-1/Rho GTPase signaling pathway

Abstract: ALEX1 expression is reduced in GC and is involved in diverse cellular functions. ALEX1 inhibits metastasis through the PAR-1/Rho GTPase signaling pathway.

Cited by 21 publications

References 32 publications

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer

Features of alternative splicing in stomach adenocarcinoma and their clinical implication: a research based on massive sequencing data

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