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Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERK signaling pathway.

ABSTRACT: Increasing emphasis has been put on the influence of desmosome related proteins on progress of colorectal cancer (CRC). Pinin (PNN) is a desmosome-associated molecule that has been reported its overexpression could increase desmoglein 2 (DSG2) and E-cadherin (E-ca) levels. However, it was documented that DSG2 and E-ca had opposite functions in CRC. Thus, we attempted to elucidate function and mechanism of PNN in CRC. Herein, we revealed that overexpression of PNN was significantly correlated with the aggressive characteristics and indicated poor overall survival of CRC patients. In addition, the proliferation, invasion in vitro, and tumorigenic growth, metastasis in vivo were also promoted by the up-regulation of PNN. It was also verified that up-regulation of PNN increased the expression of DSG2 and activated the EGFR/ERK signaling pathway. Our findings suggested that PNN, as a valuable marker of prognosis, has important influence on the progression of CRC.

SUBMITTER: Wei Z

PROVIDER: S-EPMC5045407 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERK signaling pathway.

Wei Zhigang Z Ma Wenhui W Qi Xiaolong X Zhu Xianjun X Wang Yutian Y Xu Zhuoluo Z Luo Jun J Wang Da D Guo Weihong W Li Xiaomei X Xin Sainan S Yu Jiang J Li Guoxin G

Oncotarget 20160501 20

Increasing emphasis has been put on the influence of desmosome related proteins on progress of colorectal cancer (CRC). Pinin (PNN) is a desmosome-associated molecule that has been reported its overexpression could increase desmoglein 2 (DSG2) and E-cadherin (E-ca) levels. However, it was documented that DSG2 and E-ca had opposite functions in CRC. Thus, we attempted to elucidate function and mechanism of PNN in CRC. Herein, we revealed that overexpression of PNN was significantly correlated wit ...[more]

PMID: 27107420

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Project description:To explore the relationship between miR-373 and the occurrence and development of colorectal cancer. Additionally, it aims to predict the potential cellular signaling pathways and regulatory mechanisms in which miR-373 may be involved and provides a theoretical basis and experimental evidence for the clinical application of miR-373 as a potential biomarker, molecular target, and prognostic indicator in colorectal cancer. Real-time quantitative PCR is used to analyze the expression of miR-373 in human colorectal cancer cell lines and normal human colonic epithelial cells. Further validation of the differential expression of miR-373 in colorectal cancer cell lines is being performed. Biological functions such as cell proliferation, invasion and apoptosis are being detected by MTT, CCK-8, transwell, cell cycle analysis, and flow cytometry experiments to verify the changes in the biological behavior of colon cancer cells after overexpression and interference of miR-373 in SW-480 cells and to explore the effects of miR-373 on cell proliferation, invasion, and apoptosis in colon cancer cells. Proteomic analysis is being conducted on proteins extracted from miR-373 overexpressing SW480 cells, and mass spectrometry is used for protein identification. GO, KEGG, and enrichment analysis are being employed to analyze the significantly differentially expressed proteins. The expression levels of pathway-related proteins are being verified using Western blot. Overexpression of miR-373 increased the invasive and metastatic ability of SW-480 cells; knockdown of miR-373 decreased the invasive and metastatic ability of SW-480 cells. However, there was no statistically significant effect on cell proliferation and apoptosis in SW-480 cells. Proteomic analysis identified 78 differentially expressed proteins based on fold change (FC) > 1.2 and P < 0.05. Annotation of differentially changed proteins revealed that the MAPK signaling pathway, PI3K-Akt signaling pathway, and FAK signaling pathway may play crucial roles in the migration and invasion of colorectal cancer. Western blot analysis showed that overexpression of miR-373 significantly increased the levels of p-ERK1/2 in SW480 cells. miR-373 may activate the ERK/MAPK signaling pathway to promote the invasion and migration of colorectal cancer cells.

Project description:BackgroundAs a member of the ERM (ezrin-radixin-moesin) protein family, EZR has been recognized as a regulator of adhesion signal pathways by researchers. Moreover, EZR was thought to play irreplaceable roles in invasion and metastasis of versatile cancers. In this study, we managed to undermine the effect of EZR on proliferation and metastasis in pancreatic cancer (PC).MethodsTo analyze the impact of EZR expression on overall survival and free diseases survival of PC patients, we screened abnormally expressed EZR in PC using the Gene Expression Omnibus database (GEO database) and The Cancer Genome Atlas (TCGA) database. Following, Gene Ontology (GO)-based functional analysis and Gene set enrichment analysis (GSEA) was performed to predicate the possible biological processes in which EZR were involved. The clinicopathological characteristics and prognosis of PC patients were analyzed according to clinical data. Further, immunohistochemistry, western blotting and real time PCR analysis were conducted to analyze the expression level of EZR in PC and paired paracancerous tissues. The effect of EZR on proliferation of PC cell lines were detected by Cell Counting Kit-8 assay, and meanwhile, Transwell assay was performed to detect the effect of EZR on invasion and migration of PC cell.ResultEZR exhibited higher expression level in pancreatic cancer tissues and cell than paracancerous tissues and cell, and its expression level was positively correlated with poor overall survival and diseases-free survival in PC patients. CCK8 assay indicated that EZR facilitated the proliferation of PC cells, meanwhile, Transwell assay showed that EZR promoted the migration and invasion of PC cells. The GO analysis predicated that EZR was involved in biological processes including cell adhesion, ameboidal-type cell migration, cell junction assembly. Through GSEA analysis, pancreatic cancer pathway, and the adhesion junction pathway were screened as the mostly enriched pathways in EZR-regulated pathological process. The inhibition of EZR suppressed proliferation and migration of PC cells. Western blot experiment revealed a positive correlation between EZR and FAK, the proliferation invasion and migration ability of PC cells were significantly decreased after knockdown of EZR.ConclusionOur finding revealed EZR accelerated the progression of PC via FAK/AKT signaling pathway.

Dataset Information

Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERK signaling pathway.

Publications

Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERK signaling pathway.

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