| First Author | Wang H | Year | 2023 |
| Journal | Mol Cancer Res | Volume | 21 |
| Issue | 12 | Pages | 1317-1328 |
| PubMed ID | 37606694 | Mgi Jnum | J:343708 |
| Mgi Id | MGI:7568979 | Doi | 10.1158/1541-7786.MCR-22-0808 |
| Citation | Wang H, et al. (2023) Generating a Murine PTEN Null Cell Line to Discover the Key Role of p110beta-PAK1 in Castration-Resistant Prostate Cancer Invasion. Mol Cancer Res 21(12):1317-1328 |
| abstractText | Although androgen deprivation treatment often effectively decreases prostate cancer, incurable metastatic castration-resistant prostate cancer (CRPC) eventually occurs. It is important to understand how CRPC metastasis progresses, which is not clearly defined. The loss of PTEN, a phosphatase to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate in the PI3K pathway, occurs in up to 70% to 80% of CRPC. We generated a mouse androgen-independent prostate cancer cell line (PKO) from PTEN null and Hi-Myc transgenic mice in C57BL/6 background. We confirmed that this PKO cell line has an activated PI3K pathway and can metastasize into the femur and tibia of immunodeficient nude and immunocompetent C57BL/6 mice. In vitro, we found that androgen deprivation significantly enhanced PKO cell migration/invasion via the p110beta isoform-depended PAK1-MAPK activation. Inhibition of the p110beta-PAK1 axis significantly decreased prostate cancer cell migration/invasion. Of note, our analysis using clinical samples showed that PAK1 is more activated in CRPC than in advanced prostate cancer; high PAK1/phosphorylated-PAK1 levels are associated with decreased survival rates in patients with CRPC. All the information suggests that this cell line reflects the characteristics of CRPC cells and can be applied to dissect the mechanism of CRPC initiation and progression. This study also shows that PAK1 is a potential target for CRPC treatment. IMPLICATIONS: This study uses a newly generated PTEN null prostate cancer cell line to define a critical functional role of p110beta-PAK1 in CRPC migration/invasion. This study also shows that the p110beta-PAK1 axis can potentially be a therapeutic target in CRPC metastasis. |
