Dataset Information

NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer.

ABSTRACT:

Purpose

This study aimed to investigate the effect of NPTX1 on the prognosis of gastric cancer (GC), as well as the metastatic process in GC.

Materials and methods

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the association between NPTX1 expression and prognosis in GC. Quantitative real-time polymerase chain reaction and Western blots were applied to examine the expression of NPTX1 in GC cell lines and expression of genes in downstream pathways. The role of NPTX1 on the migration, invasion, adhesion, and proliferation of GC cell lines was investigated with the transwell assay, the adhesion assay, and the MTT assay. Immunofluorescence staining was used to observe the effect of NPTX1 knockdown on the morphology of cells.

Results

According to the review of TCGA and GEO databases of GC, we found that the expression of NPTX1 increased in cancer tissues and high NPTX1 expression was correlated with poor overall survival, which was associated with lymph node stage in clinicopathologic parameters. Knockdown of NPTX1 attenuated the migration, invasion, and adhesion abilities of GC cells. According to gene set enrichment analysis, NPTX1 was found to be positively related to integrin and focal adhesion (FA). Additionally, NPTX1 knockdown decreased the expression of integrin ?1 and integrin ?7, followed by deregulation of the expression of p-Src, p-Akt, p-Erk, MMP2, and MMP7, as well as inhibiting the formation of FA complexes and decreasing the length of pseudopods in GC cells.

Conclusion

Our study provides strong evidence that NPTX1 plays a crucial role in promoting metastasis and acts as a prognostic indicator in GC.

SUBMITTER: Yan H

PROVIDER: S-EPMC6472287 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer.

Yan Hongfei H Zheng Chunlei C Li Zhi Z Bao Bowen B Yang Bowen B Hou Kezuo K Qu Xiujuan X Xiao Jiawen J Che Xiaofang X Liu Yunpeng Y

Cancer management and research 20190415

<h4>Purpose</h4>This study aimed to investigate the effect of NPTX1 on the prognosis of gastric cancer (GC), as well as the metastatic process in GC.<h4>Materials and methods</h4>The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the association between NPTX1 expression and prognosis in GC. Quantitative real-time polymerase chain reaction and Western blots were applied to examine the expression of NPTX1 in GC cell lines and expression of genes in down ...[more]

PMID: 31043800

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Project description:BackgroundThe aberrant expression of myotubularin-related protein 2 (MTMR2) has been found in some cancers, but little is known about the roles and clinical relevance. The present study aimed to investigate the roles and clinical relevance of MTMR2 as well as the underlying mechanisms in gastric cancer (GC).MethodsMTMR2 expression was examined in 295 GC samples by using immunohistochemistry (IHC). The correlation between MTMR2 expression and clinicopathological features and outcomes of the patients was analyzed. The roles of MTMR2 in regulating the invasive and metastatic capabilities of GC cells were observed using gain-and loss-of-function assays both in vitro and in vivo. The pathways involved in MTMR2-regulating invasion and metastasis were selected and identified by using mRNA expression profiling. Functions and underlying mechanisms of MTMR2-mediated invasion and metastasis were further investigated in a series of in vitro studies.ResultsMTMR2 was highly expressed in human GC tissues compared to adjacent normal tissues and its expression levels were significantly correlated with depth of invasion, lymph node metastasis, and TNM stage. Patients with MTMR2high had significantly shorter lifespan than those with MTMR2low. Cox regression analysis showed that MTMR2 was an independent prognostic indicator for GC patients. Knockdown of MTMR2 significantly reduced migratory and invasive capabilities in vitro and metastases in vivo in GC cells, while overexpressing MTMR2 achieved the opposite results. MTMR2 knockdown and overexpression markedly inhibited and promoted the epithelial-mesenchymal transition (EMT), respectively. MTMR2 mediated EMT through the IFNγ/STAT1/IRF1 pathway to promote GC invasion and metastasis. Phosphorylation of STAT1 and IRF1 was increased by MTMR2 knockdown and decreased by MTMR2 overexpression accompanying with ZEB1 down-regulation and up-regulation, respectively. Silencing IRF1 upregulated ZEB1, which induced EMT and consequently enhanced invasion and metastasis in GC cells.ConclusionsOur findings suggest that MTMR2 is an important promoter in GC invasion and metastasis by inactivating IFNγ/STAT1 signaling and may act as a new prognostic indicator and a potential therapeutic target for GC.

Dataset Information

NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer.

Purpose

Materials and methods

Results

Conclusion

Publications

NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer.

Similar Datasets

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