CD36 accelerates the progression of hepatocellular carcinoma by promoting FAs absorption

Abstract

Background: CD36 is emerging as a potential strategy for cancer treatment because of its function of regulating fatty acid intake. The purpose of this study was to clarify the molecular mechanism of CD36 in the progression of HCC.Methods: TCGA database was used to analyze the relationship of CD36 with HCC. The expression of CD36 in HCC clinical samples and cell lines was detected by qRT-PCR and western blot. Huh7 cells and HCCLM3 cells were transfected and treated into different group. CCK-8 and clone formation assay were used to detect the cell proliferation ability. Wound healing and transwell experiment were used to detect the metastatic ability. HCC xenografts were constructed in nude mice by subcutaneous injection of stably transfected Huh7 cells. The expression of CD36 in HCC was detected by immunohistochemistry (IHC). The contents of phospholipids and triglycerides in HCC cells were detected by ELISA. And the content of neutral lipids in HCC cells was detected by staining with BODIPY 493/503 and DAPI dye. Then transcriptional sequencing was used to determine the downstream mechanism of CD36 in HCC, and the differentially expressed genes (DEGs) were analyzed.Results: CD36 was up regulated in HCC. Knockdown of CD36 could suppress the proliferation and metastasis of HCC in vitro and in vivo by regulating FAs intake in HCC. In addition, the expression of AKR1C2 was suppressed by sh-CD36, and which was also involved in the regulation of FAs intake. Conclusion:The molecular mechanism by which CD36 accelerated the progression of HCC was to promote the expression of AKR1C2 and thus enhance fatty acids (FAs) intake.

Multi‐Enzyme Activity of MIL‐101 (Fe)‐Derived Cascade Nano‐Enzymes for Antitumor and Antimicrobial Therapy

“…In addition, it could be seen that Cd36 expression was down‐regulated after treatment of cancer cells with FMS NCs, indicating that the material can effectively inhibit the uptake of exogenous fatty acids and inhibit the developmental process of cancer cells. [ 58 ] Moreover, a series of target genes related to ferroptosis were also changed accordingly. FMS NCs down‐regulated the expression of Nqo1 (quinone oxidoreductase 1), which decreased intracellular glutathione levels, impaired mitochondrial function, made hepatocellular carcinoma cells more sensitive to oxidative stress, accelerated cellular deferritorialization anemia and apoptosis.…”

Altered lipid metabolism as a predisposing factor for liver metastasis in MASLD

“…In human oral carcinoma, metastasis-initiating cells express high levels of CD36 and lipid metabolism-associated genes ( Pascual et al, 2017 ). CD36 overexpression in the liver promotes HCC growth and intrahepatic metastasis through the metabolic rewiring of tumor cells ( Luo et al, 2021 , Tao et al, 2022 ). However, it remains to be elucidated whether and how the inhibition of CD36 in the context of MASLD can relieve the predisposition to liver metastases.…”

Lipid Metabolism as a Potential Target of Liver Cancer

“…Experimental evidence indicates that the upregulation of CD36 in HCC significantly enhances both proliferation and metastatic potential, both in in vitro and in vivo settings. 38 CD36, as a receptor for FAs, when deficient, leads to a reduction in FAs uptake across various human and mouse tissues. 39 Studies have revealed that the absence of CD36 notably decreases phospholipids, triglycerides, and neutral lipids in HCC cells.…”

“…Furthermore, research has shown that CD36 plays a role in regulating the proliferation and migration of HCC cells by influencing their FAs uptake. 38 Given these findings, CD36 emerges as a potential target for therapeutic intervention in HCC.…”