K604, a specific acyl-CoA:cholesterol acyltransferase 1 inhibitor, suppresses proliferation of U251-MG glioblastoma cells

Ohmoto, Takuji; Nishitsuji, Kazuchika; Yoshitani, Nobuyuki; Mizuguchi, Makoto; Yanagisawa, Yuto; Saito, Hiroyuki; Sakashita, Naomi

doi:10.3892/mmr.2015.4200

Cited by 28 publications

(26 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ACAT1 encodes a mitochondrially localized acetyl-CoA acetyltransferase. Inhibition of ACAT1 by Avasimibe inhibited cell growth by inducing cell cycle arrest and apoptosis in glioblastoma cell lines [ 6 , 55 ]. Further, inhibition of ACAT1 has also been shown to suppress growth and metastasis of pancreatic cancer [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion

Gladitz

Klink

Seifert

2018

acta neuropathol commun

View full text Add to dashboard Cite

Oligodendrogliomas are primary human brain tumors with a characteristic 1p/19q co-deletion of important prognostic relevance, but little is known about the pathology of this chromosomal mutation. We developed a network-based approach to identify novel cancer gene candidates in the region of the 1p/19q co-deletion. Gene regulatory networks were learned from gene expression and copy number data of 178 oligodendrogliomas and further used to quantify putative impacts of differentially expressed genes of the 1p/19q region on cancer-relevant pathways. We predicted 8 genes with strong impact on signaling pathways and 14 genes with strong impact on metabolic pathways widespread across the region of the 1p/19 co-deletion. Many of these candidates (e.g. ELTD1, SDHB, SEPW1, SLC17A7, SZRD1, THAP3, ZBTB17) are likely to push, whereas others (e.g. CAP1, HBXIP, KLK6, PARK7, PTAFR) might counteract oligodendroglioma development. For example, ELTD1, a functionally validated glioblastoma oncogene located on 1p, was overexpressed. Further, the known glioblastoma tumor suppressor SLC17A7 located on 19q was underexpressed. Moreover, known epigenetic alterations triggered by mutated SDHB in paragangliomas suggest that underexpressed SDHB in oligodendrogliomas may support and possibly enhance the epigenetic reprogramming induced by the IDH-mutation. We further analyzed rarely observed deletions and duplications of chromosomal arms within oligodendroglioma subcohorts identifying putative oncogenes and tumor suppressors that possibly influence the development of oligodendroglioma subgroups. Our in-depth computational study contributes to a better understanding of the pathology of the 1p/19q co-deletion and other chromosomal arm mutations. This might open opportunities for functional validations and new therapeutic strategies.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0544-y) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion

Gladitz

Klink

Seifert

2018

acta neuropathol commun

View full text Add to dashboard Cite

show abstract

“…Would inhibiting ACAT1 SOAT1 affect the progression of other human diseases? Recent results in mouse models show that ACAT1 SOAT1 is also a potential target for treating various forms of cancer (227)(228)(229). In addition, in a mouse model for atherosclerosis, a recent study showed that, in contrast to the result of knocking out ACAT1 SOAT1 in the whole body, knocking out ACAT1 SOAT1 in the myeloid cell lineage (including monocytes/macrophages, neutrophils, and eosinophils) actually reduces atherosclerotic lesions (230).…”

Section: Acat1 Soat1 Inhibitorsmentioning

confidence: 99%

Cellular cholesterol homeostasis and Alzheimer's disease

Chang

Yamauchi

Hasan

et al. 2017

Journal of Lipid Research

123

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid-β (Aβ) peptides (especially Aβ1-42) and neurofibrillary tangles, composed of hyperphosphorylated tau and accompanied by chronic neuroinflammation. Aβ peptides are derived from the amyloid precursor protein (APP). The oligomeric form of Aβ peptides is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques. ApoE is the major apolipoprotein of the lipoprotein(s) present in the CNS. ApoE has three alleles, of which the allele constitutes the major risk factor for late-onset AD. Here we describe the complex relationship between ApoE4, oligomeric Aβ peptides, and cholesterol homeostasis. The review consists of four parts:) key elements involved in cellular cholesterol metabolism and regulation; ) key elements involved in intracellular cholesterol trafficking;) links between ApoE4, Aβ peptides, and disturbance of cholesterol homeostasis in the CNS; ) potential lipid-based therapeutic targets to treat AD. At the end, we recommend several research topics that we believe would help in better understanding the connection between cholesterol and AD for further investigations.

show abstract

“…This enzyme is highly expressed in glioblastomas and in cancer of the prostate or pancreas; its expression level correlates inversely with patient survival [ 28 , 29 , 230 – 235 ]. Genetically silencing SOAT1/ACAT1 or blocking its activity using the inhibitors K604, ATR-101 or avasimibe effectively suppresses tumor growth in several cancer xenograft models [ 28 , 230 – 232 ]. These results suggest that targeting SOAT1 and cholesteryl ester synthesis may be a promising anti-cancer strategy.…”

Section: Introductionmentioning

confidence: 99%

Lipid metabolism reprogramming and its potential targets in cancer

Cheng

Geng

Cheng

et al. 2018

Cancer Communications

533

462

View full text Add to dashboard Cite

Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth. SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor, thus linking glucose metabolism and de novo lipid synthesis. Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.

show abstract

K604, a specific acyl-CoA:cholesterol acyltransferase 1 inhibitor, suppresses proliferation of U251-MG glioblastoma cells

Cited by 28 publications

References 36 publications

Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion

Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion

Cellular cholesterol homeostasis and Alzheimer's disease

Lipid metabolism reprogramming and its potential targets in cancer

Contact Info

Product

Resources

About