Overexpression of Biglycan is Associated with Resistance to Rapamycin in Human WERI-Rb-1 Retinoblastoma Cells by Inducing the Activation of the Phosphatidylinositol 3-Kinases (PI3K)/Akt/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Abstract

Background: Biglycan (BGN) is an extracellular matrix (ECM) protein that regulates the growth of epithelial cells. The mammalian target of rapamycin (mTOR) inhibitor, rapamycin, is a treatment for advanced retinoblastoma. This study aimed to investigate the effects of expression of BGN on the response of human WERI-Rb-1 retinoblastoma cells to rapamycin and to investigate the associated signaling pathways. Material/Methods: BGN gene expression was induced in human WERI-Rb-1 retinoblastoma cells, which were incubated with rapamycin at doses of 0, 5, 10, 20, 30, and 50 μg/ml. Cells were treated with the PI3K/Akt pathway inhibitor, LY294002. The MTT assay determined the rate of cell inhibition. Real-time polymerase chain reaction (RT-PCR) was performed to measure BGN gene expression using RT 2-PCR. Western blot detected the protein levels of BGN, p-PI3K, p-Akt, nuclear NF-kB, and p65. Results: Rapamycin impaired cell growth, induced cell apoptosis, and suppressed the expression levels of p-PI3K, p-Akt, nuclear NF-kB, and p65. Overexpression of the BGN gene restored growth potential and inhibited apoptosis and was associated with the activation of the PI3K/Akt-mediated NF-kB pathway. In cells that overexpressed BGN, inhibition of the PI3K/Akt pathway by LY294002 increased the sensitivity of human WERI-Rb-1 retinoblastoma cells to rapamycin. Conclusions: Overexpression of BGN induced rapamycin resistance in WERI-Rb-1 retinoblastoma cells by activating PI3K/Akt/NF-kB signaling.

PODNL1 promotes cell proliferation and migration in glioma via regulating Akt/mTOR pathway

“…Importantly, Yan et al 3 have reported PODNL1 is overexpressed in high-grade glioma and Shergalis et al 4 have indicated that PODNL1 expression is negatively correlated with overall survival. In addition, several members of the SLRP family also function as tumor suppressors via regulating PI3K/Akt/mTOR pathway 24 - 26 . Nevertheless, both the biological function and mechanism of PODNL1 in glioma remain unclear.…”

Development of a Cancer-Associated Fibroblast-Related Prognostic Model in Breast Cancer via Bulk and Single-Cell RNA Sequencing

“…Previous studies have shown the role of BGN in the treatment of drug resistance and immune activity. [27,[30][31][32]. These suggest that BGN plays an important role in tumorigenesis and metastasis.…”

Biglycan Promotes Cancer Stem Cell Properties, NFκB Signaling and Metastatic Potential in Breast Cancer Cells

“…BGN has been shown to regulate various signaling pathways in tissue specific cancers such as p38 signaling in colon cancer [ 16 ], NFκB signaling in gastric cancer [ 23 ] and PI3K-Akt-NFκB signaling axis in retinoblastomas [ 24 ]. Thus, we performed immunoblotting to identify the signaling pathways that were regulated by BGN in BCSCs.…”

“…Interestingly, we also observed that BGN inhibition in BCSCs showed enhanced chemosensitivity in presence of cisplatin and paclitaxel as compared to control cells ( Figure S7A–D ) indicating a role of BGN in chemoresistance. BGN regulates various signaling pathways such as the p38 signaling pathway in colon cancer cells and PI3K-Akt-NFκB pathway in retinoblastoma cells [ 16 , 24 ]. Consistent with previous studies showing a role of NFκB signaling in CSCs [ 36 , 37 , 38 ], we also observed the activation of NFκB pathway in CSCs, which was attenuated with loss of BGN, suggesting that this pathway is playing a major role in the tumorigenic phenotypes of BCSCs and its enrichment and metastasis.…”