The roles of Y-box-binding protein (YB)-1 and C-X-C motif chemokine ligand 14 (CXCL14) in the progression of prostate cancer via extracellular-signal-regulated kinase (ERK) signaling.

Abstract

The cold-shock protein Y-box-binding protein (YB)-1 regulates the expression of various chemokines and their receptors at the transcriptional level. Expression of the orphan chemokine CXCL14 is repressed by EGF induced signaling. The possible links between EGF-mediated YB-1 and CXCL14 as well as the functions of critical kinase pathways in the progression of prostate cancer have remained unexplored. Here we examined the correlation between YB-1 and CXCL14, and the ERK/AKT/mTOR pathways in prostate cancer. Knockdown of YB-1 decreased cyclinD1 expression with an upregulation of cleaved-PARP in human prostate cancer cells. EGF treatment upregulated phospho-YB-1 expression in a time-dependent manner, while treatment with an ERK inhibitor completely silenced its expression in prostate cancer cells. EGF treatment stimulates CyclinD1 and YB-1 phosphorylation in an ERK-dependent pathway. Positive and negative regulation of YB-1 and CXCL14 was observed after EGF treatment in prostate cancer cells, respectively. EGF rescues cell cycle and apoptosis via the AKT and ERK pathways. Furthermore, YB-1 silencing induces G1 arrest and apoptosis, while knockdown of CXCL14 facilitates cell growth and inhibits apoptosis in prostate cancer cells. YB-1 and CXCL14 were inversely correlated in prostate cancer cells and tissues. A significant association between poor overall survival and High YB-1 expression was observed in human prostate cancer patients. In conclusion, our data reveal the functional relationship between YB-1 and CXCL14 in EGF mediated ERK signaling, and YB-1 expression is a significant prognostic marker to predict prostate cancer.

• Authors: Chen Wang, Na Zhao, Fuyuki Sato, Keiji Tanimoto, Hiroyuki Okada, Yang Liu, Ujjal K Bhawal
• Journal: Bioengineered (Bioengineered) Vol. 12 Issue 2 Pg. 9128-9139 (12 2021) ISSN: 2165-5987 [Electronic] United States
• PMID: 34696665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL14 protein, human
• Chemokines, CXC
• Y-Box-Binding Protein 1
• YBX1 protein, human
• Cyclin D1
• Epidermal Growth Factor
• Poly(ADP-ribose) Polymerases
• EGFR protein, human
• ErbB Receptors

Topics

• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Chemokines, CXC (metabolism)
• Cyclin D1 (metabolism)
• Disease Progression
• Epidermal Growth Factor (pharmacology)
• ErbB Receptors (metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• MAP Kinase Signaling System (drug effects)
• Male
• Middle Aged
• Phosphorylation (drug effects)
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Signal Transduction
• Up-Regulation (drug effects)
• Y-Box-Binding Protein 1 (metabolism)