ro-3306 and Neoplasm-Metastasis

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.

Topics: Animals; CDC2 Protein Kinase; Cell Cycle; Cell Cycle Proteins; Epithelial-Mesenchymal Transition; Glycogen Synthase Kinase 3 beta; Male; MAP Kinase Signaling System; Mice; Mice, Nude; Microtubule-Associated Proteins; Neoplasm Metastasis; Phosphorylation; Prognosis; Prostatic Neoplasms; Quinolines; Snail Family Transcription Factors; Thiazoles; Xenograft Model Antitumor Assays