C/EBPβ LIP augments cell death by inducing osteoglycin

Wassermann-Dozorets, Rina; Rubinstein, Menachem

doi:10.1038/cddis.2017.155

Cited by 7 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So, it was not a surprise that OGN expression was markedly associated with longer survival time, with prolonged cancer specific survival as 75.7 months in the High OGN expression group versus 61.6 months in the Low OGN expression group. In addition, the OGN promoter contains three conserved AP-1-binding sites [ 19 ], prompting the validation of OGN as a target gene downstream to LIP/MAPK/AP-1 [ 20 ]. Then cell death can be induced by activating MAPK/AP-1 and OGN expression.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

J Exp Clin Cancer Res

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Autophagy is another mechanism responsible for mediating cellular organelles and function by OGN expression. As OGN promoter containing three conserved AP-1-binding sites [ 22 ], it was validated that OGN acted as a target gene downstream to LIP/MAPK/AP-1 [ 23 ]. So specific knockdown of OGN mRNA could attenuated cell death and autophagy triggered by ER stress in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Osteoglycin-induced VEGF Inhibition Enhances T Lymphocytes Infiltrating in Colorectal Cancer

Hu¹,

Li²,

Li³

et al. 2018

EBioMedicine

View full text Add to dashboard Cite

BackgroundOGN could modify tissue inflammation and immune response via local and circulating innate immune cells, which was suggestive of a reciprocal relationship between OGN and T cell infiltration in cancer. Hence, we aim to measure the OGN expression patterns and immune cells response in colorectal cancer(CRC).MethodsThis study enrolled three independent sets of patients from TCGA and the Fudan University Shanghai Cancer Center(FUSCC). The effect of OGN on T cell infiltration and the mechanism were examined in vitro and in vivo.FindingsTumor OGN expression levels were positively associated with CD3, CD8, and PTPRC expressions in the training and testing sets from TCGA, respectively. In validation set from FUSCC, OGN expression level also paralleled positively with CD8+ cell density in colorectal cancer tissue (p < .001). For a unit decrease in outcome quartile categories, multivariable OR in the lowest (vs highest) OGN expression was 0.17 (95% CI 0.08–0.33). Consistently, immunofluorescence validated that OGN was preferentially expressed with CD8+ cells in both normal epithelium and cancer tissue. Xenograft tumors arising from MC38 cells with OGN-over-expression displayed a significant increase in CD8+ cells recruitment. Hence, high expression of OGN was associated with a profound longer survival (P = .009). In mechanism, elevated OGN expression inhibited the activation of the transcriptional genes HIF-1α in CRC cells, then significantly impeded the expression of VEGF. As a result of this, T cell tumor infiltration was reduced.InterpretationOGN expression is positively associated with CD8+ cell density in colorectal cancer tissue, suggesting a possible influence of OGN expression on tumor reactive T cells in the tumor niche.FundNo

show abstract

“…In murine hepatocarcinoma, overexpression of OGN in Hca-F cells by plasmid DNA transfection decreased the cells’ lymphatic metastatic potential both in vitro and in vivo 22. Meanwhile, tumor-suppressor activity was observed in mouse melanoma cell lines as overexpression of OGN increased stress-triggered cell death while reduction of OGN attenuated cell death 23. Despite these studies indicating that OGN expression is reduced in tumors, further research is necessary to elucidate the nature of OGN’s function in the pathology of cancer, especially breast cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>Osteoglycin (OGN) Inhibits Cell Proliferation and Invasiveness in Breast Cancer via PI3K/Akt/mTOR Signaling Pathway</p>

Zhang

Dong

et al. 2019

OTT

View full text Add to dashboard Cite

IntroductionPrevious studies have indicated that the small leucine-rich proteoglycan (SLR) osteoglycin (OGN) is downregulated in various cancers, including squamous cervical carcinoma, gastric cancer, and colorectal adenoma, indicating that OGN is a putative tumor suppressor. However, its exact role in the pathology of human cancers, especially breast cancer (BC), is not clear.MethodsThe expression of OGN in BC tissues was examined using qRT-PCR. Online databases were employed to analyze the correlation between OGN expression and clinicopathological characteristics. CCK-8 assay, colony formation assay, transwell migration and invasion assays were applied to detect cell proliferation, colony formation, migration and invasion of BC cells, respectively. Xenograft tumor models were constructed to explore the role of OGN on tumor growth in vivo.ResultsOGN expression was reduced in 24 paired BC samples compared with normal tissue. Decreased expression of OGN was correlated with greater pathological grade, a more aggressive tumor subtype, and poor overall survival. In vitro experiments showed that OGN overexpressed by plasmid transfection significantly inhibited cell proliferation, colony formation, migration, and invasion of BC cell lines. In xenograft tumor models, overexpression of OGN repressed the growth of MCF-7 cells in vivo and alleviated the compression of the tumor on surrounding structures. We also observed that OGN expression reversed EMT via repressing the PI3K/Akt/mTOR pathway.ConclusionThis study revealed that OGN could function as a tumor suppressor during breast carcinogenesis, and we contribute new evidence to the body of research on the SLRP family.

show abstract

C/EBPβ LIP augments cell death by inducing osteoglycin

Cited by 7 publications

References 47 publications

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

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

Osteoglycin-induced VEGF Inhibition Enhances T Lymphocytes Infiltrating in Colorectal Cancer

<p>Osteoglycin (OGN) Inhibits Cell Proliferation and Invasiveness in Breast Cancer via PI3K/Akt/mTOR Signaling Pathway</p>

Contact Info

Product

Resources

About