ArticleJournal of experimental & clinical cancer research : CR2023
PINK1-PTEN axis promotes metastasis and chemoresistance in ovarian cancer via non-canonical pathway.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Non-coding RNAs' pivotal importance in modulation of cancer sensitivity to Topotecan: a systematic review.Medical oncology (Northwood, London, England) · 2025Pooled it
- A genome-wide Mendelian randomization study focusing on endoplasmic reticulum stress reveals novel genetic markers for renal cell carcinoma.Oncology letters · 2026Article
- A prognostic model for breast cancer based on mitochondria-associated endoplasmic reticulum membrane (MAM) signature genes.Discover oncology · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies.European journal of medical research · 2025Review
- Article
- A mitochondrial permeability transition-associated lncRNA signature predicts prognosis and the immune response in gastric cancer.Hereditas · 2025Article
- CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology.Science advances · 2025Article
- Evaluation of PINK1 protein expression as a predictive marker for the efficacy of adjuvant chemotherapy in colorectal cancer: a retrospective study.BMC gastroenterology · 2025Article
- Evaluating the Antitumor Potential of Cannabichromene, Cannabigerol, and Related Compounds fromInternational journal of molecular sciences · 2025Article
- PI3K and PINK1 Immunoexpression as Predictors of Survival in Patients Undergoing Resection of Brain Metastases from Lung Adenocarcinoma.International journal of molecular sciences · 2025Article
- Selective anti-cancer effects of cannabidiol and Δ9-tetrahydrocannabinol via PI3K/AKT/mTOR inhibition and PTEN restoration in ovarian cancer cells.Frontiers in pharmacology · 2025Article
- Unraveling the role of long non-coding RNAs in therapeutic resistance in acute myeloid leukemia: New prospects & challenges.Non-coding RNA research · 2024Review
- PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells.Cancer research communications · 2024Article
- Targeting cellular mitophagy as a strategy for human cancers.Frontiers in cell and developmental biology · 2024Review
- Review
- Research progress in endometriosis-associated ovarian cancer.Frontiers in oncology · 2024Review
- Post-Translational Modification of PTEN Protein: Quantity and Activity.Oncology reviews · 2024Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundOvarian cancer is commonly associated with a poor prognosis due to metastasis and chemoresistance. PINK1 (PTEN-induced kinase 1) is a serine/threonine kinase that plays a crucial part in regulating various physiological and pathophysiological processes in cancer cells.
methodsThe ATdb database and "CuratedOvarianData" were used to evaluate the effect of kinases on ovarian cancer survival. The gene expression in ovarian cancer cells was detected by Western blot and quantitative real-time PCR. The effects of gene knockdown or overexpression in vitro were evaluated by wound healing assay, cell transwell assay, immunofluorescence staining, immunohistochemistry, and flow cytometry analysis. Mass spectrometry analysis, protein structure analysis, co-immunoprecipitation assay, nuclear-cytoplasmic separation, and in vitro kinase assay were applied to demonstrate the PINK1-PTEN (phosphatase and tensin homolog) interaction and the effect of this interaction. The metastasis experiments for ovarian cancer xenografts were performed in female BALB/c nude mice.
resultsPINK1 was strongly associated with a poor prognosis in ovarian cancer patients and promoted metastasis and chemoresistance in ovarian cancer cells. Although the canonical PINK1/PRKN (parkin RBR E3 ubiquitin protein ligase) pathway showed weak effects in ovarian cancer, PINK1 was identified to interact with PTEN and phosphorylate it at Serine179. Remarkably, the phosphorylation of PTEN resulted in the inactivation of the phosphatase activity, leading to an increase in AKT (AKT serine/threonine kinase) activity. Moreover, PINK1-mediated phosphorylation of PTEN impaired the nuclear import of PTEN, thereby enhancing the cancer cells' ability to resist chemotherapy and metastasize.
conclusionsPINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. PINK1 promotes ovarian cancer metastasis and chemotherapy resistance through the regulation of PTEN. These findings offer new potential therapeutic targets for ovarian cancer management.
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