CD36 tango in cancer: signaling pathways and functions

Abstract

CD36, a scavenger receptor expressed in multiple cell types, mediates lipid uptake, immunological recognition, inflammation, molecular adhesion, and apoptosis. CD36 is a transmembrane glycoprotein that contains several posttranslational modification sites and binds to diverse ligands, including apoptotic cells, thrombospondin-1 (TSP-1), and fatty acids (FAs). Beyond fueling tumor metastasis and therapy resistance by enhancing lipid uptake and FA oxidation, CD36 attenuates angiogenesis by binding to TSP-1 and thereby inducing apoptosis or blocking the vascular endothelial growth factor receptor 2 pathway in tumor microvascular endothelial cells. Moreover, CD36-driven lipid metabolic reprogramming and functions in tumor-associated immune cells lead to tumor immune tolerance and cancer development. Notable advances have been made in demonstrating the regulatory networks that govern distinct physiological properties of CD36, and this has identified targeting CD36 as a potential strategy for cancer treatment. Here, we provide an overview on the structure, regulation, ligands, functions, and clinical trials of CD36 in cancer.

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

“…Three genes were prominently modulated by the different species: CD36, IL6 , and TNF- α. CD36 is an important transmembrane protein receptor which involved in regulating immune response, cell adhesion and lipid metabolism. CD36 plays an important role in cancer by accelerating tumor growth and metastasis, and modulating the immune response and response to therapy, and has thus been a target for cancer treatment (Wang and Li, 2019 ). Recently, Sakurai et al ( 2020 ) have demonstrated the role of CD36 in facilitating the proliferation and migration activity of OSCC cells, possibly by inhibiting β-catenin signaling pathway, and they emphasized its usefulness in the diagnosis of high-grade tumor and targeted therapy of oral cancer.…”

Comment on Aasebø, E., et al. “The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles”. Cancers 2020, 12, 1466

“…Therefore, we speculate that this specific mutation may confer a survival advantage to neoplastic cells, since wild type CD36 has been shown to be involved in apoptosis by activation of caspase 3 [ 4 ]. In summary, we have independently identified an unrecognized CD36/Y235* mutation in a case of AML by NGS, which underscores the strength of this technology to decipher genetic alterations and further supports a possible oncogenic role of CD36 [ 2 ].…”

“…In a recent article published in this journal, Aasebø and colleagues reported [ 1 ] increased levels of various proteins, including CD36, in acute myeloid leukemia (AML) cells at relapse, when compared with the time of first presentation, and suggest targeting these proteins for direct therapeutic strategies to alleviate chemoresistance in relapsed AML. Interestingly, CD36 is a scavenger receptor that mediates lipid uptake, and is gaining attention in clinical trials as a potential druggable target in cancer treatment [ 2 ]. Using next generation sequencing (NGS) in a bone marrow specimen from a patient with AML and synchronous plasma cell myeloma, we have identified a CD36/Y325* mutation, which would encode a truncated protein lacking the signaling intracytoplasmic carboxyl-terminus end.…”

Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate

“…Therefore, CD36 may be a potential target for cancer treatment. Although several preclinical studies and clinical trials targeting CD36 for cancer treatment are being performed [88], further studies are needed to explore the effects of CD36 on innate immune cell-mediated anti-tumor functions. It has been shown that palmitoylation of CD36 enhances fatty acid uptake activity and stabilizes its plasma membrane translocation [89].…”