<scp>PP2A</scp> methylesterase <scp>PME</scp>‐1 suppresses anoikis and is associated with therapy relapse of <scp><i>PTEN</i></scp>‐deficient prostate cancers

Aakula, Anna; Isomursu, Aleksi; Rupp, Christian; Erickson, Andrew; Gupta, Nikhil; Kauko, Otto; Shah, Pragya; Padzik, Artur; Pokharel, Yuba Raj; Kaur, Amanpreet; Li, Song-Ping; Trotman, Lloyd C.; Taimen, Pekka; Rannikko, Antti; Lammerding, Jan; Paatero, Ilkka; Mirtti, Tuomas; Ivaska, Johanna; Westermarck, Jukka

doi:10.1002/1878-0261.13353

Cited by 6 publications

(2 citation statements)

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“…For the zebrafish in vivo dissemination assay, the siCTRL and siSIX2 cells were injected in zebrafish vein and the invaded cells were measured after 24 h similarly as before ( 27 ). Briefly, PC-3 cells were washed with PBS, stained with CellTracker Green CMFDA dye (5 μm, Thermo Fisher Scientific) and detacher and detached with trypsin–EDTA in a single incubation step at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer

Leppänen,

Kaljunen,

Takala

et al. 2024

Nucleic Acids Research

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The use of androgen receptor (AR) inhibitors in prostate cancer gives rise to increased cellular lineage plasticity resulting in resistance to AR-targeted therapies. In this study, we examined the chromatin landscape of AR-positive prostate cancer cells post-exposure to the AR inhibitor enzalutamide. We identified a novel regulator of cell plasticity, the homeobox transcription factor SIX2, whose motif is enriched in accessible chromatin regions after treatment. Depletion of SIX2 in androgen-independent PC-3 prostate cancer cells induced a switch from a stem-like to an epithelial state, resulting in reduced cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects were mediated through the downregulation of the Wnt/β-catenin signalling pathway and subsequent reduction of nuclear β-catenin. Collectively, our findings provide compelling evidence that the depletion of SIX2 may represent a promising strategy for overcoming the cell plasticity mechanisms driving antiandrogen resistance in prostate cancer.

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Section: Methodsmentioning

confidence: 99%

SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer

Leppänen,

Kaljunen,

Takala

et al. 2024

Nucleic Acids Research

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“…The high heterogeneity of PCa makes treatment response, drug resistance, and clinical outcomes unpredictable (Wang et al., 2022 ). Identifying new biomarkers for early intervention and developing targeted cancer control interventions are crucial to reduce PCa mortality (Aakula et al., 2023 ; Siegel et al., 2023 ). Recent studies have shown that PCa is associated with recurrent somatic mutations, copy number variations (CNV), and chromosomal rearrangements (Li, Liu, et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of a novel anoikis‐related prognostic model for prostate cancer

Zhang,

Lv,

Luan

et al. 2024

Molec Gen & Gen Med

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BackgroundAnoikis resistance is a hallmark characteristic of oncogenic transformation, which is crucial for tumor progression and metastasis. The aim of this study was to identify and validate a novel anoikis‐related prognostic model for prostate cancer (PCa).MethodsWe collected a gene expression profile, single nucleotide polymorphism mutation and copy number variation (CNV) data of 495 PCa patients from the TCGA database and 140 PCa samples from the MSKCC dataset. We extracted 434 anoikis‐related genes and unsupervised consensus cluster analysis was used to identify molecular subtypes. The immune infiltration, molecular function, and genome alteration of subtypes were evaluated. A risk signature was developed using Cox regression analysis and validated with the MSKCC dataset. We also identify potential drugs for high‐risk group patients.ResultsTwo subtypes were identified. C1 exhibited a higher level of CNV amplification, immune score, stromal score, aneuploidy score, homologous recombination deficiency, intratumor heterogeneity, single‐nucleotide variant neoantigens, and tumor mutational burden compared to C2. C2 showed a better survival outcome and had a high level of gamma delta T cell and activated B cell infiltration. The risk signature consisting of four genes (HELLS, ZWINT, ABCC5, and TPSB2) was developed (area under the curve = 0.780) and was found to be an independent prognostic factor for overall survival in PCa patients. Four CTRP‐derived and four PRISM‐derived compounds were identified for high‐risk patients.ConclusionsThe anoikis‐related prognostic model developed in this study could be a useful tool for clinical decision‐making. This study may provide a new perspective for the treatment of anoikis‐related PCa.

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Transcriptome analysis revealed that PME-1 suppresses inflammatory signaling, activates PI3K/Akt signaling, and promotes epithelial-mesenchymal transition

Ikeda,

Sato,

Ohama

2024

Biochemical and Biophysical Research Communications

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PP2A methylesterase PME‐1 suppresses anoikis and is associated with therapy relapse of PTEN‐deficient prostate cancers

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 6 publications

References 58 publications

SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer

SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer

Identification and validation of a novel anoikis‐related prognostic model for prostate cancer

Transcriptome analysis revealed that PME-1 suppresses inflammatory signaling, activates PI3K/Akt signaling, and promotes epithelial-mesenchymal transition

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