ArticleOncotarget2017
Diet-induced obesity links to ER positive breast cancer progression via LPA/PKD-1-CD36 signaling-mediated microvascular remodeling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Arteriolar angiogenesis: implications in anti-angiogenic immunotherapy for pancreatic cancers.Cytokine & growth factor reviews · 2025Review
- Clinical Relationship Between Serum ApoB, HER2, and Myocardial Ischemia Risk in Breast Cancer Patients.Cancer reports (Hoboken, N.J.) · 2025Article
- Inside anticancer therapy resistance and metastasis. Focus on CD36.Journal of Cancer · 2024Review
- Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity.Cells · 2022Article
- CD36 and Its Role in Regulating the Tumor Microenvironment.Current oncology (Toronto, Ont.) · 2022Review
- Role of CD36 in cancer progression, stemness, and targeting.Frontiers in cell and developmental biology · 2022Review
- Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease.International journal of molecular sciences · 2021Review
- Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling.Communications biology · 2021Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.Signal transduction and targeted therapy · 2021Review
- Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective.Frontiers in cell and developmental biology · 2021Review
- Obesity Inhibits Angiogenesis Through TWIST1-SLIT2 Signaling.Frontiers in cell and developmental biology · 2021Article
- Editorial: Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity.Frontiers in cell and developmental biology · 2021Article
- The Role of Diet in Cancer Prevention and Chemotherapy Efficacy.Annual review of nutrition · 2020Review
- Review
- Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention.Advanced drug delivery reviews · 2020Review
- Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice.Frontiers in oncology · 2020Article
- Role of Hippo-YAP Signaling in Osseointegration by Regulating Osteogenesis, Angiogenesis, and Osteoimmunology.Frontiers in cell and developmental biology · 2020Review
- Heterogeneity of Vascular Endothelial Cells, De Novo Arteriogenesis and Therapeutic Implications in Pancreatic Neuroendocrine Tumors.Journal of clinical medicine · 2019Review
- VEGF/PKD-1 signaling mediates arteriogenic gene expression and angiogenic responses in reversible human microvascular endothelial cells with extended lifespan.Molecular and cellular biochemistry · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity increases cancer risk including breast cancer (BC). However, the direct regulatory mechanisms by which obesity promotes BC progression remain largely unknown. We show that lysophosphatidic acid/protein kinase D1 (LPA/PKD-1)-CD36 signaling is a bona fide breast cancer promoter via stimulating microvascular remodeling in chronic diet-induced obesity (DIO). We observed that the growth of an estrogen receptor (ER) positive breast cancer was markedly increased when compared to the lean control, and specifically accompanied by increased microvascular remodeling in a syngeneic BC model in female DIO mice. The tumor neovessels in DIO mice demonstrated elevated levels of alpha smooth muscle actin (α-SMA), vascular endothelial growth factor receptor 2 (VEGFR 2) and endothelial differentiation gene 2/LPA receptor1 (Edg2/LPA1), enhanced PKD-1 phosphorylation, and reduced CD36 expression. Tumor associated endothelial cells (TAECs) exposed to LPA demonstrated sustained nuclear PKD-1 phosphorylation, and elevated mRNA levels of ephrin B2, and reduced mRNA expression of CD36. TAEC proliferation also increased in response to LPA/PKD-1 signaling. These studies suggest that the LPA/PKD-1-CD36 signaling axis links DIO to malignant progression of BC via stimulation of de novo tumor arteriogenesis through arteriolar remodeling of microvasculature in the tumor microenvironment. Targeting this signaling axis could provide an additional novel therapeutic strategy.
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