Subtopic Deep Dive
CD36 Receptor in Cancer Lipid Uptake
Research Guide
What is CD36 Receptor in Cancer Lipid Uptake?
CD36 is a scavenger receptor that mediates fatty acid uptake in cancer cells, promoting tumor metastasis, survival, and immune evasion through lipid metabolism reprogramming.
CD36 facilitates long-chain fatty acid transport into tumor cells, enhancing energy supply and membrane synthesis during metastasis (Luo et al., 2017). Studies validate CD36's role in breast, prostate, and bone cancers using blocking antibodies and knockout models. Over 10 papers from 2003-2024 link CD36 to ferroptosis resistance and lipid droplet formation, with key works cited over 500 times.
Why It Matters
CD36 inhibition blocks fatty acid uptake, reducing metastasis in prostate and breast cancer models (Herroon et al., 2013; Luo et al., 2017). It dampens CD8+ T cell function via ferroptosis in tumors, impairing immunotherapy (Ma et al., 2021). As a biomarker for advanced disease, CD36 targeting overcomes drug resistance linked to adipocyte lipid supply (Cao, 2019). Therapeutic antibodies show promise in preclinical trials.
Key Research Challenges
Targeting Metastatic Niches
CD36 drives pre-metastatic niche formation by enabling fatty acid uptake from adipocytes (Herroon et al., 2013). Blocking antibodies reduce tumor growth in bone metastasis models but face delivery issues in vivo. Clinical translation requires models mimicking human lipid environments (Luo et al., 2017).
Ferroptosis Immune Evasion
CD36 mediates ferroptosis resistance in tumor cells and CD8+ T cells, suppressing antitumor immunity (Ma et al., 2021). Lipid peroxidation mechanisms remain unclear despite GPX4 links (Feng and Stockwell, 2018). Balancing ferroptosis induction without harming immune effectors challenges therapy design (Zhou et al., 2024).
Lipid Droplet Heterogeneity
CD36 promotes lipid droplet biogenesis for cancer hallmarks like survival and signaling (Cruz et al., 2020). Droplet composition varies by cancer type, complicating universal inhibitors. PPAR regulation adds crosstalk with metabolism pathways (Lefèbvre, 2006).
Essential Papers
Reprogramming of fatty acid metabolism in cancer
Nikos Koundouros, George Poulogiannis · 2019 · British Journal of Cancer · 1.5K citations
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Philippe Lefèbvre · 2006 · Journal of Clinical Investigation · 934 citations
PPARalpha is a nuclear receptor that regulates liver and skeletal muscle lipid metabolism as well as glucose homeostasis. Acting as a molecular sensor of endogenous fatty acids (FAs) and their deri...
Lipid metabolism and cancer
Xueli Bian, Rui Liu, Ying Meng et al. · 2020 · The Journal of Experimental Medicine · 913 citations
Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signa...
Minireview: Lipid Metabolism, Metabolic Diseases, and Peroxisome Proliferator-Activated Receptors
Chih‐Hao Lee, Peter Olson, Ronald M. Evans · 2003 · Endocrinology · 871 citations
Lipid and carbohydrate homeostasis in higher organisms is under the control of an integrated system that has the capacity to rapidly respond to metabolic changes. The peroxisome proliferator-activa...
CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability
Xingzhe Ma, Liuling Xiao, Lintao Liu et al. · 2021 · Cell Metabolism · 840 citations
Unsolved mysteries: How does lipid peroxidation cause ferroptosis?
Huizhong Feng, Brent R. Stockwell · 2018 · PLoS Biology · 717 citations
Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairi...
Emerging roles of lipid metabolism in cancer metastasis
Xiangjian Luo, Can Cheng, Zheqiong Tan et al. · 2017 · Molecular Cancer · 692 citations
Reading Guide
Foundational Papers
Start with Lefèbvre (2006, 934 cites) for PPAR-CD36 lipid sensing basics, then Herroon et al. (2013, 205 cites) for adipocyte-tumor FA transfer in bone metastasis models.
Recent Advances
Ma et al. (2021, 840 cites) on CD36-ferroptosis in T cells; Cruz et al. (2020, 503 cites) on lipid droplets; Zhou et al. (2024, 510 cites) on therapeutic strategies.
Core Methods
Fatty acid-BSA tracing, CD36 antibodies (sulfo-N-succinimidyl oleate), scRNA-seq for expression, PPAR luciferase assays, ferroptosis inducers like erastin.
How PapersFlow Helps You Research CD36 Receptor in Cancer Lipid Uptake
Discover & Search
Research Agent uses searchPapers('CD36 fatty acid uptake cancer metastasis') to find Luo et al. (2017) with 692 citations, then citationGraph reveals clusters linking to Ma et al. (2021) on ferroptosis. exaSearch uncovers niche papers like Herroon et al. (2013) on bone marrow adipocytes.
Analyze & Verify
Analysis Agent applies readPaperContent on Ma et al. (2021) to extract CD36-ferroptosis data, then verifyResponse with CoVe cross-checks claims against Bian et al. (2020). runPythonAnalysis processes lipid uptake rates from supplements using pandas for statistical verification; GRADE scores evidence as high for metastasis links.
Synthesize & Write
Synthesis Agent detects gaps in CD36-PPAR crosstalk from Lefèbvre (2006) and flags contradictions in ferroptosis roles. Writing Agent uses latexEditText for methods sections, latexSyncCitations for 20+ refs, and latexCompile to generate a review manuscript with exportMermaid diagrams of uptake pathways.
Use Cases
"Extract and plot CD36 expression vs metastasis rates from breast cancer datasets in recent papers"
Research Agent → searchPapers → Analysis Agent → runPythonAnalysis (pandas/matplotlib on supplementary data from Luo et al. 2017) → researcher gets CSV plots of correlation stats (r=0.75, p<0.01).
"Draft LaTeX figure caption and cite CD36 antibody experiments for prostate cancer review"
Synthesis Agent → gap detection → Writing Agent → latexGenerateFigure + latexSyncCitations (Herroon et al. 2013) → researcher gets compiled PDF snippet with tumor growth curves.
"Find GitHub repos analyzing CD36 lipid models from ferroptosis papers"
Research Agent → paperExtractUrls (Ma et al. 2021) → Code Discovery → paperFindGithubRepo + githubRepoInspect → researcher gets 3 repos with Python sims of fatty acid uptake kinetics.
Automated Workflows
Deep Research workflow scans 50+ papers via searchPapers on 'CD36 cancer lipid uptake', chains citationGraph to Herroon et al. (2013), and outputs structured report with GRADE scores. DeepScan's 7-steps verify ferroptosis claims (Ma et al., 2021) using CoVe checkpoints and runPythonAnalysis on peroxidation data. Theorizer generates hypotheses on CD36-PPAR synergies from Lefèbvre (2006) and Cruz et al. (2020).
Frequently Asked Questions
What is the definition of CD36's role in cancer lipid uptake?
CD36 is a transmembrane receptor enabling fatty acid uptake in tumor cells, fueling metastasis and survival (Luo et al., 2017).
What methods validate CD36 in cancer models?
Blocking antibodies and CD36 knockout reduce metastasis in breast/prostate xenografts; lipid tracing shows uptake dependency (Herroon et al., 2013).
What are key papers on CD36 in cancer?
Luo et al. (2017, 692 cites) on metastasis; Ma et al. (2021, 840 cites) on ferroptosis; Cruz et al. (2020, 503 cites) on lipid droplets.
What open problems exist in CD36 research?
Clinical antibody delivery to metastatic niches; resolving ferroptosis dual roles in tumors vs immunity; tumor-type lipid specificity (Zhou et al., 2024).
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Part of the Cancer, Lipids, and Metabolism Research Guide