ArticleBreast cancer research : BCR2023
PAQR8 promotes breast cancer recurrence and confers resistance to multiple therapies.
Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial.Nature medicine · 2025Trial
- CRISPR screening identifies DTX4 governing alveolar macrophage cholesterol efflux in pulmonary alveolar proteinosis.JCI insight · 2026Article
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- BUB1B promotes homologous recombination‑mediated DNA damage repair in breast cancer cells through the PI3K/AKT signaling pathway.Oncology reports · 2025Article
- Comprehensive Genetic Map of Muscle Lipidome Reveals Novel Insights Into Flavor Variation in Ruminant Meat.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Selection Signature Analysis of Whole-Genome Sequences to Identify Genome Differences Between Selected and Unselected Holstein Cattle.Animals : an open access journal from MDPI · 2025Article
- CD44 Marks Dormant Tumor Cells After HER2 Inhibition in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Unraveling the Mystery of Breast Cancer Dormancy: Insights into Genetic, Receptor, and Cellular Interactions Driving Late Recurrence.Frontiers in immunology · 2025Review
- Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy.Breast cancer research : BCR · 2024Article
- Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination.Genome medicine · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Decoding TROP2 in breast cancer: significance, clinical implications, and therapeutic advancements.Frontiers in oncology · 2023Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBreast cancer mortality is principally due to recurrent disease that becomes resistant to therapy. We recently identified copy number (CN) gain of the putative membrane progesterone receptor PAQR8 as one of four focal CN alterations that preferentially occurred in recurrent metastatic tumors compared to primary tumors in breast cancer patients. Whether PAQR8 plays a functional role in cancer is unknown. Notably, PAQR8 CN gain in recurrent tumors was mutually exclusive with activating ESR1 mutations in patients treated with anti-estrogen therapies and occurred in > 50% of both patients treated with anti-estrogen therapies and those treated with chemotherapy or anti-Her2 agents.
methodsWe used orthotopic mouse models to determine whether PAQR8 overexpression or deletion alters breast cancer dormancy or recurrence following therapy. In vitro studies, including assays for colony formation, cell viability, and relative cell fitness, were employed to identify effects of PAQR8 in the context of therapy. Cell survival and proliferation were quantified by immunofluorescence staining for markers of apoptosis and proliferation. Sphingolipids were quantified by liquid chromatography-high resolution mass spectrometry.
resultsWe show that PAQR8 is necessary and sufficient for efficient mammary tumor recurrence in mice, spontaneously upregulated and CN gained in recurrent tumors that arise following therapy in multiple mouse models, and associated with poor survival following recurrence as well as poor overall survival in breast cancer patients. PAQR8 promoted resistance to therapy by enhancing tumor cell survival following estrogen receptor pathway inhibition by fulvestrant or estrogen deprivation, Her2 pathway blockade by lapatinib or Her2 downregulation, and treatment with chemotherapeutic agents. Pro-survival effects of PAQR8 were mediated by a G
conclusionsOur data provide in vivo evidence that PAQR8 plays a functional role in cancer, implicate PAQR8, cAMP, and ceramide metabolism in breast cancer recurrence, and identify a novel mechanism that may commonly contribute to the acquisition of treatment resistance in breast cancer patients.
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