2020
DOI: 10.1038/s41389-020-0226-z
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ACSL4 promotes hepatocellular carcinoma progression via c-Myc stability mediated by ERK/FBW7/c-Myc axis

Abstract: Hepatocellular carcinoma (HCC) is a highly heterogeneous, multigene-driven malignant tumor. Long chain acyl-CoA synthetase 4 (ACSL4), an enzyme has pivotal roles in arachidonic acid (AA) metabolism. However, its function and the underlying molecular mechanisms in HCC are still not fully elucidated. Here, we identified ACSL4 as a novel marker for AFP high subtype HCC through transcriptome profiling. ACSL4 was frequently upregulated in HCC samples and associated with poor prognosis. Functionally, ACSL4 knockdown… Show more

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Cited by 68 publications
(67 citation statements)
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“…The absence of NFAT2 in carcinoma tissues would enhance the activation of AKT and ERK. The activated ERK could phosphorylate Ser62 site in c-myc and thus stabilize the c-myc [28], while the activation of AKT promoted COX-2 expression and COX-2 dependent pro-metastasis [29]. In the current study, the expression of c-myc and COX-2 was obviously increased in carcinoma tissues, which was in agree with the previous research and our deduction.…”
Section: Discussionsupporting
confidence: 92%
“…The absence of NFAT2 in carcinoma tissues would enhance the activation of AKT and ERK. The activated ERK could phosphorylate Ser62 site in c-myc and thus stabilize the c-myc [28], while the activation of AKT promoted COX-2 expression and COX-2 dependent pro-metastasis [29]. In the current study, the expression of c-myc and COX-2 was obviously increased in carcinoma tissues, which was in agree with the previous research and our deduction.…”
Section: Discussionsupporting
confidence: 92%
“…Interestingly, ACSL4 and ALOX5 were found to be significantly up-regulated in HCC patients with high CIFI values, even though they facilitate the execution of ferroptosis ( Liu et al, 2015 ; Yuan et al, 2016 ; Doll et al, 2017 ). However, it is worth noting that both ACSL4 and ALOX5 are over-expressed in HCC as compared to normal livers, and promote the progression of the disease ( Xu et al, 2011 ; Chen et al, 2020 ; Ndiaye et al, 2020 ; Wang et al, 2020 ). Thus, the over-expression of ACSL4 and ALOX5 contributes to the proliferation and progression of HCC, but renders the patients more susceptible to ferroptosis inducers.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to regulating the synthesis and degradation of lipids, ACSL4 has been found overexpressed in several origins of cancer [50][51][52]. It is noteworthy that ACSL4 favors tumor progression in HCC via stabilization of the oncoprotein c-myc through the ubiquitin-proteasome system [53], and the mRNA expression of ACSL4 in HepG2 cells was substantially higher than that in Hep3B cells [53] which is in accordance with the gene expression pattern obtained from the Cancer Cell Line Encyclopedia database (data not shown). Therefore, the higher sensitivity of HepG2 cells to FC-induced ferroptosis may be, at least in part, attributed to the higher expression of ACSL4.…”
Section: Discussionmentioning
confidence: 99%