Background
Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved.
Material/Methods
Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3β-β/catenin pathway was detected by western blot.
Results
OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3β-β/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells.
Conclusions
OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3β-β/catenin pathway.
BackgroundGastric cancer (GC) is one of the most common malignancies in digestive system, among which the differentiation of diffuse type GC is relatively poor, the probability of distant metastasis and lymph node metastasis is relatively high, and the clinical prognosis is relatively poor. The purpose of this study is to explore potential signaling pathways and key biomarkers that drive the development of diffuse type GC. Methods Using the “limma” package in R to screen Differentially expressed genes. Screening hub genes by PPI analysis. Immunohistochemistry analysis and qRT-PCR analysis was carried out to detect genes expression. Using Kaplan-Meier Plotter database analyzed the prognostic roles of hub genes.ResultsA total of 355 DEGs consisting of 293 diffuse type DEGs and 62 intestinal type DEGs were selected according to screening criteria, 3 hub genes were chosen from diffuse type DEGs according to the degree of connectivity by using protein-protein interaction (PPI) networks and Cytoscape software including AGT, CXCL12 and ADRB2. Immunohistochemistry analysis and qRT-PCR results showed that the expression of three genes was related to the different GC lauren types. The Kaplan Meier analysis showed that the expression values of these three genes were related to prognosis of diffuse type GC. ConclusionsAGT, CXCL12 and ADRB2 might contribute to the progression of diffuse type GC, which could have potential as biomarkers or therapeutic targets for diffuse type GC.
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