The CD36 Knockout 786-O Polyclonal Cells product consists of a heterogeneous pool of 786-O cells that have undergone CRISPR/Cas9-mediated disruption of the CD36 gene, leading to a loss-of-function model for studying CD36-dependent processes.
The 786-O cell line originates from a primary clear cell renal cell carcinoma and is characterized by a VHL mutation resulting in stabilization and overexpression of HIF-2alpha, a hallmark of the pseudohypoxic state driving tumor progression. This genetic background renders the cells particularly relevant for investigating interactions between metabolic adaptation and oncogenic signaling in kidney cancer.
CD36 functions as a multifunctional scavenger receptor that mediates the uptake of oxidized LDL and long-chain fatty acids, thereby linking extracellular lipid supply to intracellular signaling cascades. It is transcriptionally regulated by PPAR-gamma, LXR, and HIF-1alpha, and its activity is modulated by interacting partners such as thrombospondin-1, integrins (including alphaVbeta3 and alpha6beta1), and tetraspanins CD9 and CD81. Upon ligand engagement, CD36 activates downstream effectors including Src family kinases, VAV, Rac1, the MAPK cascade (p38, JNK, and ERK), and NF-kB, promoting lipid droplet formation, inflammatory gene expression, and angiogenic programs. In 786-O cells, this receptor is constitutively active due to elevated HIF-1alpha and TNF-alpha levels, sustaining a feed-forward loop of lipid uptake and pro-survival signaling.
Given the 786-O line??s VHL deficiency and HIF-2alpha overexpression, CD36 loss-of-function disrupts a key nexus between hypoxia-driven lipid scavenging and oncogenic signaling. CD36 knockout in these cells is expected to significantly reduce oxidized LDL uptake and fatty acid import, thereby attenuating lipid droplet accumulation??a phenotype often associated with clear cell renal cell carcinoma. This metabolic rewiring likely impairs activation of the NF-kB and MAPK pathways, diminishing the production of pro-inflammatory cytokines and angiogenic factors such as VEGF. Furthermore, CD36 disruption may interfere with thrombospondin-1-mediated TGF-beta activation and integrin crosstalk, potentially reducing invasive capacity. Consequently, this polyclonal knockout pool serves as a powerful tool to dissect how lipid metabolism fuels tumor aggression in a VHL-mutant, HIF-driven background, and to identify synthetic vulnerabilities arising from the loss of CD36-dependent lipid handling.
Researchers can utilize this polyclonal CD36 knockout cell population to investigate functional roles of CD36 in renal carcinoma lipid metabolism and tumor progression. Typical applications include western blotting and RT-qPCR to confirm disruption of CD36 expression, flow cytometry to quantify uptake of fluorescently labeled oxidized LDL, and immunofluorescence microscopy to visualize lipid droplet accumulation. Functional assays such as Boyden chamber migration and invasion, angiogenesis tube formation with endothelial cells, and metabolic flux analysis using Seahorse technology can delineate CD36??s contribution to metastatic and angiogenic phenotypes. Additionally, these cells enable drug sensitivity screens (MTT, colony formation) to identify compounds whose efficacy is CD36-dependent. For further technical details, lot-specific knockout validation data, and ordering information, please contact Ascent Research.
