TPX2 mediates prostate cancer epithelial-mesenchymal transition through CDK1 regulated phosphorylation of ERK/GSK3β/SNAIL pathway

• Published in: Biochemical and biophysical research communications 2021-03, Vol.546, p.1-6
• Main Authors: Zhang, Boya, Zhang, Mingpeng, Li, Qi, Yang, Yanjie, Shang, Zhiqun, Luo, Jun
• Format: Article
• Language: English
• Subjects: Animals; CDC2 Protein Kinase - antagonists & inhibitors; CDC2 Protein Kinase - metabolism; CDK1; Cell Cycle; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - deficiency; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; EMT; Epithelial-Mesenchymal Transition - drug effects; ERK/GSK3β/SNAIL; Glycogen Synthase Kinase 3 beta - metabolism; High gleason grade prostate cancer; Male; MAP Kinase Signaling System - drug effects; Mice; Mice, Nude; Microtubule-Associated Proteins - antagonists & inhibitors; Microtubule-Associated Proteins - deficiency; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neoplasm Metastasis - drug therapy; Phosphorylation - drug effects; Prognosis; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Quinolines - pharmacology; Snail Family Transcription Factors - metabolism; Thiazoles - pharmacology; TPX2; Xenograft Model Antitumor Assays
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.01.106

Prostate cancer with high Gleason grade is prone to metastasis, which is one of the factors that seriously threaten the survival of patients, and it is also a treatment difficulty. In this study, we first revealed the potential connection between TPX2 and prostate cancer metastasis. We found that TPX2 is highly expressed in high-grade prostate cancer and is significantly related to poor prognosis. Depletion of TPX2 can significantly inhibit cell activity and migration, and in vivo experiments show that knockdown of TPX2 can significantly inhibit tumor growth. In terms of mechanism, we found that knocking down TPX2 can inhibit the expression of CDK1, repress the phosphorylation of ERK/GSK3β/SNAIL signaling pathway, and thereby inhibit tumor epithelial-mesenchymal transition. Subsequently, we found that after rescuing TPX2, all related proteins and phenotype changes were restored, and this effect can be inhibited by CDK1 inhibitor, RO-3306. Our findings suggest the potential of TPX2 as an important target in anti-tumor metastasis therapy, which is conducive to precision medicine for prostate cancer. •High expression of TPX2 is related to the prognosis of high Gleason grade prostate cancer.•TPX2 not only regulates the cell cycle in prostate cancer, but is also related to metastasis.•In vivo and in vitro experiments show that TPX2 depletion can inhibit tumor epithelial-mesenchymal transition.•TPX2 affects ERK/GSK3β/SNAIL phosphorylation by regulating CDK1.•The rescue experiment can restore the changes caused by TPX2 depletion.