Aakula_2023_Mol.Oncol_17_1007

Reference

Title : PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers - Aakula_2023_Mol.Oncol_17_1007
Author(s) : Aakula A , Isomursu A , Rupp C , Erickson A , Gupta N , Kauko O , Shah P , Padzik A , Pokharel YR , Kaur A , Li SP , Trotman L , Taimen P , Rannikko A , Lammerding J , Paatero I , Mirtti T , Ivaska J , Westermarck J
Ref : Mol Oncol , 17 :1007 , 2023
Abstract : While organ-confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumours with concomitant inhibition of two tumour suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having < 50% 5-year secondary-therapy-free patient survival. Functionally, overexpression of PME-1, a methylesterase for the catalytic PP2A-C subunit, inhibits anoikis in PTEN-deficient PCa cells. In vivo, PME-1 inhibition increased apoptosis in in ovo PCa tumour xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME-1-deficient PC3 cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype known to correlate with increased apoptosis sensitivity. In summary, our results demonstrate that PME-1 supports anoikis resistance in PTEN-deficient PCa cells. Clinically, these results identify PME-1 as a candidate biomarker for a subset of particularly aggressive PTEN-deficient PCa.
ESTHER : Aakula_2023_Mol.Oncol_17_1007
PubMedSearch : Aakula_2023_Mol.Oncol_17_1007
PubMedID: 36461911
Gene_locus related to this paper: human-PPME1

Related information

Gene_locus related to this paper: human-PPME1

Citations formats

Aakula A, Isomursu A, Rupp C, Erickson A, Gupta N, Kauko O, Shah P, Padzik A, Pokharel YR, Kaur A, Li SP, Trotman L, Taimen P, Rannikko A, Lammerding J, Paatero I, Mirtti T, Ivaska J, Westermarck J (2023)
PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers
Mol Oncol 17 :1007

Aakula A, Isomursu A, Rupp C, Erickson A, Gupta N, Kauko O, Shah P, Padzik A, Pokharel YR, Kaur A, Li SP, Trotman L, Taimen P, Rannikko A, Lammerding J, Paatero I, Mirtti T, Ivaska J, Westermarck J (2023)
Mol Oncol 17 :1007