ArticleCancer research2016
Ovarian Cancer Chemoresistance Relies on the Stem Cell Reprogramming Factor PBX1.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 71 citations in OpenAlex.
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- The chromatin landscape of high-grade serous ovarian cancer metastasis identifies regulatory drivers in post-chemotherapy residual tumour cells.Communications biology · 2024Article
- M6A-methylated circPOLR2B forms an R-loop and regulates the biological behavior of glioma stem cells through positive feedback loops.Cell death & disease · 2024Article
- The emerging role of JAK inhibitors in ovarian cancer: new kids on the block?Annals of medicine and surgery (2012) · 2024Article
- PBX1: a TALE of two seasons-key roles during development and in cancer.Frontiers in cell and developmental biology · 2024Review
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- Secreted Soluble Factors from Tumor-Activated Mesenchymal Stromal Cells Confer Platinum Chemoresistance to Ovarian Cancer Cells.International journal of molecular sciences · 2023Article
- Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer.Oncogenesis · 2023Article
- Comprehensive overview of the role of PBX1 in mammalian kidneys.Frontiers in molecular biosciences · 2023Review
- PBX1 attenuates HCell stress & chaperones · 2022Article
- Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Article
- The regulation of PBXs and their emerging role in cancer.Journal of cellular and molecular medicine · 2022Review
- Matrix Metalloproteinases in Chemoresistance: Regulatory Roles, Molecular Interactions, and Potential Inhibitors.Journal of oncology · 2022Review
- PBX1: a key character of the hallmarks of cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Development of small molecule inhibitors targeting PBX1 transcription signaling as a novel cancer therapeutic strategy.iScience · 2021Article
- PBX1-directed stem cell transcriptional program drives tumor progression in myeloproliferative neoplasm.Stem cell reports · 2021Article
- Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy.Journal of translational medicine · 2020Article
- PBX1 Increases the Radiosensitivity of Oesophageal Squamous Cancer by Targeting of STAT3.Pathology oncology research : POR · 2020Article
- Development of a nomogram to predict prognosis in ovarian cancer: a SEER-based study.Translational cancer research · 2020Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The evolution of chemoresistance is a fundamental characteristic of cancer that ultimately hampers its clinical management. However, it may be possible to improve patient outcomes significantly by a better understanding of resistance mechanisms, which cancers rely upon during the evolution to an untreatable state. Here we report an essential role of the stem cell reprogramming factor, PBX1, in mediating chemoresistance in ovarian carcinomas. In the clinical setting, high levels of PBX1 expression correlated with shorter survival in post-chemotherapy ovarian cancer patients. In tumor cells with low endogenous levels of PBX1, its enforced expression promoted cancer stem cell-like phenotypes, including most notably an increase in resistance to platinum-based therapy used most commonly for treating this disease. Conversely, silencing PBX1 in platinum-resistant cells that overexpressed PBX1 sensitized them to platinum treatment and reduced their stem-like properties. An analysis of published genome-wide chromatin immunoprecipitation data indicated that PBX1 binds directly to promoters of genes involved in stem cell maintenance and the response to tissue injury. We confirmed direct regulation of one of these genes, STAT3, demonstrating that the PBX1 binding motif at its promoter acted to positively regulate STAT3 transcription. We further demonstrated that a STAT3/JAK2 inhibitor could potently sensitize platinum-resistant cells to carboplatin and suppress their growth in vivo Our findings offer a mechanistic rationale to target the PBX1/STAT3 axis to antagonize a key mechanism of chemoresistance in ovarian cancers and possibly other human cancers. Cancer Res; 76(21); 6351-61. ©2016 AACR.
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