CLC-3 and SOX2 regulate the cell cycle in DU145 cells

Abstract

Sex determining region Y-box 2 (SOX2) is a transcription factor that serves a role in numerous different types of malignant cancer. Altered expression of chloride channel proteins has been described in a variety of malignancies. However, the association between SOX2 and chloride channel proteins is not yet fully understood. The present study investigated the association between SOX2 and chloride voltage-gated channel 3 (CLC-3) in prostate cancer. Flow cytometry demonstrated that the inactivation of CLC-3 or SOX2 arrested cell cycle progression in the G 0 /G 1 phase. Furthermore, CLC-3 was observed to bind to SOX2, and vice versa, by co-immunoprecipitation. SOX2 appears to initiate and maintain prostate cancer tumorigenesis, in part, by modulating the cell cycle. These findings indicate the potential of SOX2 and CLC-3 as targets for the development of multi-targeted therapeutics.

SOX2 regulates paclitaxel resistance of A549 non‑small cell lung cancer cells via promoting transcription of ClC‑3

“…SOX2 promotes ClC-3 transcription. Our previous study revealed that SOX2 interacts with ClC-3 in DU145 prostatic carcinoma cells and contributes to tumorigenesis (30). To further examine whether there was a potential interaction between ClC-3 and SOX2 in PTX-resistant A549 NSCLC cells, the interaction of SOX2 and ClC-3 was detected using an IP assay.…”

“…Our previous study showed that SOX2 regulates the progression of prostate cancer cells by interacting with ClC-3 ( 30 ); however, there was no interaction between SOX2 and ClC-3 in PTX-resistant A549 NSCLC cells. Furthermore, ClC-3 is a downstream molecule of SOX2; however, SOX2 expression was increased following transfection with siClC-3 and SOX2 expression was decreased by ClC-3 overexpression.…”

ClC‐c regulates the proliferation of intestinal stem cells via the EGFR signalling pathway in Drosophila

“… 45 A recent study has shown that, in DU145 prostate cancer cells, ClC‐3 also acts as a signalling molecule that directly interacts with the stem cell factor SOX2, and then, the two co‐regulate the cell cycle. 46 Regulation of the cell cycle is very important for stem cell self‐renewal. However, it is still unknown whether ClC‐3 is involved in the regulation of adult stem cells.…”

ClC-3: A Novel Promising Therapeutic Target for Atherosclerosis

“…28 For example, ClC-3 mediated Cl À efflux is likely to elicit effects on activation of the intra-endosomal signaling pathway, including BCl-2/Bax, 29 AKT/GSK3b, 30 PI3K/AKT/ mTOR/p70S6 K, 31 JNK/p38 MAPK, 15 CXCR4/JAK-2, 32 ERK1/2, 33 Beclin1/Vps34, 34 and Wnt/b-catenin. 35 Moreover, ClC-3 may be a critical subunit or cooperative protein for the assembly of functional proteins or membrane receptors, such as NADPH oxidase 1 (NOX1), 36 protein kinase C (PKC), 37 calcium/calmodulin-dependent protein kinase II (CamKII), 21 matrix metalloproteinase-2 (MMP-2) receptors, 38 Sirtuin 1 (Sirt1), 39 SRY-box transcription factor 2 (SOX2), 40 and serumand glucocorticoid-regulated kinase 1 (SGK1). 41 Notably, angiotensin II (AngII), lipopolysaccharide (LPS), interleukin (IL), endothelin 1 (ET1), transforming growth factor-b1 (TGF-b1), and tumor necrosis factor-a (TNF-a) can promote the ClC-3 expression and stimulate the activation of multiple inflammatory signaling pathways such as nuclear factor kappa B (NF-kB), 36,42 Janus kinase (JAK)-signal transducer and activator of transcription (STAT), 43 and LPS/ Toll-like receptor 4 (TLR4).…”