Lipid raft involvement in signal transduction in cancer cell survival, cell death and metastasis

Li, Borui; Qin, Yi; Yu, Xianjun; Xu, Xiaowu; Yu, Wenyan

doi:10.1111/cpr.13167

Cited by 53 publications

(48 citation statements)

References 112 publications

(185 reference statements)

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“…Compared to the surrounding membrane, lipid rafts exhibit a more ordered and tightly packed structure. Lipid rafts are involved in various biological events, such as protein transport and apoptosis, because they provide a stable platform and contribute to the mediation and amplification of various cellular signals [ 29 , 30 ]. In the present study, MβCD was administered to disrupt intact lipid rafts.…”

Section: Discussionmentioning

confidence: 99%

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE−/− Mice

Liu

Teishima

Fu-jian

et al. 2022

Cells

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Lipid rafts play important roles in signal transduction, particularly in responses to inflammatory processes. The current study aimed to identify whether lipid raft-mediated inflammation contributes to hyperhomocysteinemia (HHcy)-accelerated atherosclerosis (AS), and to investigate the underlying mechanisms. THP-1-derived macrophages were used for in vitro experiments. ApoE−/− mice were fed a high-fat diet for 12 weeks to establish an AS model, and a high-fat plus high-methionine diet was used to induce HHcy. We found that homocysteine (Hcy) increased the expression of p22phox and p67phox and promoted their recruitment into lipid rafts (indicating the assembly of the NOX complex), thereby increasing ROS generation and NOX activity, NLRP3 inflammasome activation, and pyroptosis. Mechanistically, Hcy activated the NOX-ROS-NLRP3 inflammasome pathway and induced pyroptosis by increasing the expression of acid sphingomyelinase (ASM) to promote the formation of lipid raft clustering. Importantly, lipid raft-mediated pyroptosis was confirmed in HHcy mice, and HHcy-promoted macrophage recruitment in atherosclerotic lesions and HHcy-aggravated AS were blocked by the lipid raft disruptor methyl-β-cyclodextrin. The study findings indicate that Hcy promotes lipid raft clustering via the upregulation of ASM, which mediates the assembly of the NOX complex, causing an increase in ROS generation, NLRP3 inflammasome activation, and pyroptosis, and contributes to HHcy-induced AS.

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Section: Discussionmentioning

confidence: 99%

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE−/− Mice

Liu

Teishima

Fu-jian

et al. 2022

Cells

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“…Therefore, it may be possible to reverse the status of the immune desert by targeting B3GALT4 in NB cells. Lipid rafts, plasma membrane microdomains enriched in gangliosides, play a significant role in regulating signaling pathways and cancer progression [57][58][59]. Previous studies have reported that the gangliosides GD3 and GM1 are associated with lipid raft formation [36,37].…”

Section: Discussionmentioning

confidence: 99%

B3GALT4 remodels the tumor microenvironment through GD2-mediated lipid raft formation and the c-met/AKT/mTOR/IRF-1 axis in neuroblastoma

Sha

Liu

Yang

et al. 2022

J Exp Clin Cancer Res

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Background Beta-1,3-galactosyltransferase-4 (B3GALT4) plays a critical regulatory role in tumor biology. However, the role of B3GALT4 in modulating the tumor microenvironment (TME) of neuroblastoma (NB) remains unknown. Methods Public datasets and clinical NB samples were collected to evaluate the expression and clinical significance of GD2 and B3GALT4 in NB patients. CCK-8, colony formation, and transwell assays and experiments in tumor-bearing mouse models were conducted to investigate the function of B3GALT4. Flow cytometry, ELISA, immunohistochemistry, immunofluorescence, western blotting, and chemotaxis assays were conducted to ascertain the immunomodulatory mechanism of B3GALT4. The combined therapeutic effect of the lipid raft inhibitor MβCD and anti-GD2 mAb was validated in a murine model of NB. Results GD2 was overexpressed in NB tissues and high expression of GD2 was associated with poor prognosis in NB patients. B3GALT4 was downregulated in NB tissues, and low expression of B3GALT4 indicated poor prognosis in NB patients. Silencing B3GALT4 significantly enhanced tumor progression both in vitro and in vivo. Meanwhile, the overexpression of B3GALT4 increased the recruitment of CD8+ T lymphocytes via the chemokines CXCL9 and CXCL10. Additionally, B3GALT4 regulated NB-cell GD2 expression and lipid raft formation. Mechanistically, B3GALT4 regulated the expression of CXCL9 and CXCL10 via the c-Met signaling in the lipid rafts and the downstream AKT/mTOR/IRF-1 pathway. The lipid raft inhibitor, MβCD, attenuated B3GALT4 deficiency-induced tumor progression and immune evasion. Last, MβCD combined with anti-GD2 mAb treatment significantly enhanced the antitumor effect and the infiltration of CD8+ T cells. Conclusions Upregulation of B3GALT4 promotes the secretion of CXCL9 and CXCL10 to recruit CD8+ T lymphocytes via the GD2-mediated lipid rafts and the c-Met/AKT/mTOR/IRF-1 pathway. Moreover, lipid raft inhibitors may enhance the efficacy of anti-GD2 immunotherapy for NB.

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“…Lipid rafts are cholesterol- and sphingolipid-enriched membrane domains containing specific proteins for specialized cellular functions. Lipid rafts are involved in the signal transduction in cancer cell survival, cell death, and metastasis [ 31 ]. Alterations of lipid rafts are also linked to age-associated neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease [ 32 ].…”

Section: Cholesterol Homeostasismentioning

confidence: 99%

Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds

Liou

Mani

Yen

2022

IJMS

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Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis.

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Lipid raft involvement in signal transduction in cancer cell survival, cell death and metastasis

Cited by 53 publications

References 112 publications

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE−/− Mice

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE−/− Mice

B3GALT4 remodels the tumor microenvironment through GD2-mediated lipid raft formation and the c-met/AKT/mTOR/IRF-1 axis in neuroblastoma

Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds

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