PLPP1 suppreses breast cancer tumor growth
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ABSTRACT:
PROVIDER: PRJNA527811 | ENA |
REPOSITORIES: ENA
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Project description:PLPP1 is kncoked down by shRNA in SUM159, a triple negative breast cancer cell line, and the resulting transcriptome change are investigated.
2025-12-20 | GSE128468 | GEO
Project description:Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis, in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts represent the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for newly diagnosed women; orthotopic breast tumor grafting marks a step toward individualized models for tumor growth, metastasis, and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer. Single replicates of genomic DNA from 12 human breast cancer tumors and xenografts of those tumors in immunodeficient mice were hybridized to Affymetrix Human SNP 6.0 genotyping arrays.
2011-10-22 | E-GEOD-32530 | biostudies-arrayexpress
Project description:Hormone receptor (HR) positive breast cancer, defined by expression of estrogen (ER) and/or progesterone (PR) receptor expression, is the most commonly diagnosed type of breast cancer. PR alters the transcriptional landscape to support tumor growth in concert with or independent of ER. Understanding the mechanisms regulating PR function are critical to developing new strategies to treat HR+ breast cancer. O-GlcNAc is a post-translational modification responsible for nutrient sensing that fine tunes protein function. We have previously reported O-GlcNAcylation on PR. Although PR is heavily post translationally modified, primarily through phosphorylation, specific sites of O-GlcNAcylation on PR, and how they regulate PR action, have not been investigated. Using established PR-expressing breast cancer cell lines, we mapped the sites of O-GlcNAcylation on PR. RNA-sequencing revealed site-specific O-GlcNAcylation of PR is critical for ligand-independent suppression of interferon signaling, a regulatory function of PR previously studied in our lab. Furthermore, O-GlcNAcylation of PR enhances PR-driven tumor growth in vivo. We have delineated one mechanism regulating PR function in breast cancer that impacts tumor growth, and provided additional insight into the mechanism through which PR attenuates interferon signaling.
2024-06-17 | MSV000095057 | MassIVE
Project description:Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis, in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts represent the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for newly diagnosed women; orthotopic breast tumor grafting marks a step toward individualized models for tumor growth, metastasis, and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer.
2011-10-23 | GSE32530 | GEO
Project description:Programmed death ligand-1 (PD-L1) is a well-known transmembrane protein, which antibodies present effective clinical therapy in multiple human cancers. However, the function of tumor cell-intrinsic PD-L1 and its related mechanism in breast cancer remains incompletely studied. Programmed death ligand 1 (PD-L1) on the membrane of tumor cells strengthens tumor immune escape. Tumor cell-intrinsic PD-L1 is also involved in tumorigenesis and development, but the mechanism in regulating PD-L1 expression remains incompletely studied. Here, we report a novel mechanism for PD-L1 that can be induced by hepatitis B X-interacting protein (HBXIP), an oncogenic transcriptional coactivator, promoting breast cancer growth. Overexpression of PD-L1 increases breast cancer proliferation in vitro and in vivo. Transcriptomic analysis also reveals that PD-L1 plays a critical role in cancer development. Furthermore, we find that the expression of PD-L1 is positively associated with HBXIP in breast cancer clinical tissues as well as in cell lines, PD-L1 and HBXIP expression have higher levels in tumor. Mechanistically, HBXIP predominantly stimulates the promoter activity of PD-L1 through coactivating transcription factor ETS2. Especially, HBXIP induced PD-L1 acetylation with the acetyltransferase p300 at lysine 270 (K270), enhancing PD-L1 protein stability. Functionally, depletion of HBXIP markedly attenuates PD-L1-induced breast tumor growth in vitro and in vivo. Moreover, aspirin decreased breast cancer growth via targeting PD-L1 and HBXIP. Taken together, our results extend a new mechanism of PD-L1 functions, expound non-immune effects of PD-L1 and imply broader uses for PD-L1 as a target in breast cancer therapy.
2022-02-02 | GSE158696 | GEO
Project description:Metabolic programming plays a crucial role in T-cell activation. Herein, we describe how phospholipid metabolism regulates CD8+ T-cell function in patients with cancer. We found that phosphatidylcholine (PC) and phosphatidyl ethanolamine (PE) levels were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. The expression of phospholipid phosphatase 1 (PLPP1), an enzyme that catalyzes PE and PC synthesis, was also downregulated in CD8+ T cells upon infiltrating tumors. Moreover, unsaturated fatty acid-mediated ferroptosis was a major factor impairing the antitumor function of PLPP1-deficient CD8+ T cells infiltrated in tumors, accompanied by enhanced reactive oxygen species production and lipid peroxidation. The activation of programmed cell death 1 (PD-1) signaling in CD8+ T cells suppressed the PLPP1 expression by increasing GATA1 binding to the promoter region of PLPP1. PLPP1 expression was upregulated after anti-PD-1 therapy. Our findings revealed therapeutic potential of enhancing PLPP1 levels to restore CD8+ T-cell function.
2024-03-19 | GSE261644 | GEO
Project description:Metabolic programming plays a crucial role in T-cell activation. Herein, we describe how phospholipid metabolism regulates CD8+ T-cell function in patients with cancer. We found that phosphatidylcholine (PC) and phosphatidyl ethanolamine (PE) levels were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. The expression of phospholipid phosphatase 1 (PLPP1), an enzyme that catalyzes PE and PC synthesis, was also downregulated in CD8+ T cells upon infiltrating tumors. Moreover, unsaturated fatty acid-mediated ferroptosis was a major factor impairing the antitumor function of PLPP1-deficient CD8+ T cells infiltrated in tumors, accompanied by enhanced reactive oxygen species production and lipid peroxidation. The activation of programmed cell death 1 (PD-1) signaling in CD8+ T cells suppressed the PLPP1 expression by increasing GATA1 binding to the promoter region of PLPP1. PLPP1 expression was upregulated after anti-PD-1 therapy. Our findings revealed therapeutic potential of enhancing PLPP1 levels to restore CD8+ T-cell function.
2024-03-19 | GSE261642 | GEO
Project description:Metabolic programming plays a crucial role in T-cell activation. Herein, we describe how phospholipid metabolism regulates CD8+ T-cell function in patients with cancer. We found that phosphatidylcholine (PC) and phosphatidyl ethanolamine (PE) levels were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. The expression of phospholipid phosphatase 1 (PLPP1), an enzyme that catalyzes PE and PC synthesis, was also downregulated in CD8+ T cells upon infiltrating tumors. Moreover, unsaturated fatty acid-mediated ferroptosis was a major factor impairing the antitumor function of PLPP1-deficient CD8+ T cells infiltrated in tumors, accompanied by enhanced reactive oxygen species production and lipid peroxidation. The activation of programmed cell death 1 (PD-1) signaling in CD8+ T cells suppressed the PLPP1 expression by increasing GATA1 binding to the promoter region of PLPP1. PLPP1 expression was upregulated after anti-PD-1 therapy. Our findings revealed therapeutic potential of enhancing PLPP1 levels to restore CD8+ T-cell function.
2024-05-17 | GSE262231 | GEO
Project description:Carolina Breast Cancer Study tumor expression
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Project description:Hepsin, a type II transmembrane serine protease, is commonly overexpressed in prostate and breast cancer. The hepsin protein is stabilized by the Ras-MAPK pathway, and downstream, this protease regulates the degradation of extracellular matrix components and activates growth factor pathways, such as hepatocyte growth factor and transforming growth factor beta (TGFβ) pathway. However, how exactly active hepsin promotes cell proliferation machinery to sustain tumor growth is not fully understood. Here, we show that genetic deletion of Hpn in a WAP-Myc model of aggressive MYC-driven breast cancer inhibits tumor growth in the primary syngrafted sites and the growth of disseminated tumors in the lungs. The suppression of tumor growth upon loss of hepsin was accompanied by downregulation of TGFβ and EGFR signaling together with a reduction in EGFR protein levels. We further demonstrate in 3D cultures of patient-derived breast cancer explants that neutralizing antibodies and small-molecule inhibitors of hepsin can be used to mitigate the hepsin-induced TGFβ signaling and reduce EGFR protein levels.The study demonstrates a role for hepsin as a regulator of cell proliferation and tumor growth through TGFβ and EGFR pathways, warranting consideration of hepsin as a potential indirect upstream target for therapeutic inhibition of TGFβ and EGFR pathways in cancer.
2023-10-30 | GSE245265 | GEO