Androgen receptor‑mediated upregulation of quaking affects androgen receptor‑related prostate cancer development and anti‑androgen receptor therapy

Abstract

The androgen receptor (AR) has a crucial role in prostate cancer. RNA-binding protein-mediated post-transcriptional regulation is important in the initiation and development of cancer. The present study attempted to elucidate the mutual association of AR and RNA-binding protein quaking (QKI) in the development of prostate cancer. Dual-luciferase reporter demonstrated that AR can positively regulate the expression of QKI in prostate cancer cell lines due to its effective transcription regulating function. In addition, QKI may increase expression of AR by heat shock protein 90, which is a coactivator of AR, and silencing QKI can increase the sensitive of Casodex, which is an antagonist of AR in castration-resistant prostate cancer. This may be a new strategy for advanced prostate cancer.

Updates on Overcoming Bicalutamide Resistance: A Glimpse into Resistance to a Novel Antiandrogen

“…When an RNA-binding protein called quaking (QKI) increases the concentration of heat shock protein 90, AR consequently becomes activated. As mentioned before, enhanced AR activity is associated with resistance phenotype; therefore, inhibition of QKI protein is capable of increasing cancerous cells’ sensitivity to bicalutamide . Contrarily, loss of AR expression or downstream signaling pathway may lead to bicalutamide resistance.…”

“…As mentioned before, enhanced AR activity is associated with resistance phenotype; therefore, inhibition of QKI protein is capable of increasing cancerous cells' sensitivity to bicalutamide. 24 Contrarily, loss of AR expression or downstream signaling pathway may lead to bicalutamide resistance. It is believed that the explanation lies in cells having no dependency on AR signaling and hypermethylation of the AR gene promoter caused by genetic factors which can block AR expression.…”

Global Gene Expression Characterization of Circulating Tumor Cells in Metastasic Castration-Resistant Prostate Cancer Patients

“…On the other hand, the QKI gene codifies for Quaking protein, which has important signal transduction and RNA activation functions. In PC, positive AR expression often co-exists with higher QKI expression levels [ 48 ]. The expression of FGD4 is also upregulated in PC and is associated with the increased aggressiveness of the disease.…”

Integrins and Actions of Androgen in Breast Cancer

“…To form a ligand-AR complex and to control gene expression 2. To stimulate the proliferation of prostate cancer cells [12] ERα ER-positive breast cancer To stimulate the proliferation of ER-positive breast cancer cells [9] Integrin αv Prostate cancer To regulate tumor cell migration and growth [13] Integrin β1 Hepatocellular carcinoma To induce cell adhesion through PI3K/AKT signaling pathway [14] Integrin β1C Prostate cancer To be correlated with prostate cancer progression [15] Integrin α2 Prostate cancer To regulate metastasis mediated by adhesion to ColI through RANKL/RANK signaling [16] Table 1. Cont.…”