Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway

Abstract

BackgroundMany types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, and the role of OGN in cancer progression.MethodsThe tissue microarray staining was performed and the relevance between OGN expression and oncologic outcomes was performed using Cox regression analysis. The effect of OGN on cell proliferation and tumorigenesis was examined in vitro and in vivo. Immunoprecipitation assay, immunofluorescence analysis and internalization assay were used for mechanistic study.ResultsPatients with high expression of OGN were associated with a profound longer survival in CRC and the high serum OGN level was also indicative of fewer recurrences consistently. In colon cancer cells, OGN increased dimerization of EGFR, then triggered EGFR endocytosis and induced the recruitment of downstream components of the EGFR internalization machinery (Eps15 and epsin1). Above all, OGN reduced Zeb-1 expression via EGFR/Akt leading to inhibition of epithelial-mesenchymal transition. As results, in vitro and in vivo, the OGN expression was demonstrated to reduce cell proliferation, inhibit invasion of colon cancer cells then impede cancer progression.ConclusionsThere is a positive association between OGN level and prolonged survival in CRC. OGN plays a restrictive role in colorectal cancer progression by reduced activation of EGFR/AKT/Zeb-1.

Analysis of the Interaction Network of Hub miRNAs-Hub Genes, Being Involved in Idiopathic Pulmonary Fibers and Its Emerging Role in Non-small Cell Lung Cancer

“…Different signal pathways should be activated to regulate or influence OGN. Although many studies identified that the expression levels of OGN would alter in cancers, such as gastric cancer (Lee et al, 2003), colorectal cancer (Hu et al, 2018), and invasive ductal breast carcinoma (Roewer et al, 2011), functional data about how OGN participating in cancer pathology are not enough, and further studies are needed.…”

Osteoglycin – A switch from angiogenesis to T-cell recruitment?

“…Available expression data collectively suggest that OGN acts as a tumor suppressor, but functional analysis demonstrating the specific mechanisms through which OGN affects tumor progression is essentially lacking. In this issue of EBiomedicine, Hu and co-authors demonstrate a novel mechanism through which OGN limits tumor growth in colorectal cancer, namely through enhancing T-lymphocyte recruitment [ 2 ].…”

“…High intratumoral expression of OGN is associated with prolonged patient survival in colorectal cancer, originally attributed to an inhibition of epithelial-mesenchymal transition (EMT) and reduced tumor invasiveness [ 2 ]. In the present study, Hu et al demonstrate a correlation between OGN expression and T-cell infiltration in human tumors by combining expression data from publicly available databases and in-house patient cohorts.…”

A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome

“…Given the high number of cancer types exhibiting a coordinated expression decrease (or increase) of these core secretome genes, we reasoned that these genes would likely be responsible for important tumor-specific functions. Many of the genes exhibiting decreased expression are putative or established tumor suppressors (e.g., ANGPTL1, C2orf40, CHRDL1, OGN, C7, GREM2) ( Hu et al, 2018 ; Kuo et al, 2013 ; Li et al, 2015 ; Pei et al, 2017 ; Tsubamoto et al., 2016 ; Ying et al, 2016 ), are involved in the remodeling of the extracellular matrix (ECM) (e.g., DNASE1L3, CLEC3B, PI16, CCBE1) ( Barton et al, 2010 ; Hawes et al., 2015 ; Hazell et al, 2016 ; Obrist et al, 2004 ), and/or participate in cell-matrix adhesion functions (e.g., MFAP4, DPT, MAMDC2) ( Avilés-Vázquez et al, 2017 ; Pilecki et al, 2016 ; Yamatoji et al, 2012 ).…”