Inhibition of fatty acid synthase suppresses neovascularization via regulating the expression of VEGF-A in glioma

Zhou, Yiqiang; Jin, Guishan; Mi, Ruifang; Zhang, Junwen; Zhang, Jin; Xu, Hengzhou; Cheng, Sen; Zhang, Yunsheng; Song, Wenjie; Liu, Fusheng

doi:10.1007/s00432-016-2249-6

Cited by 25 publications

(31 citation statements)

References 32 publications

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“…The significant impact of FASN inhibitors on angiogenesis has also been demonstrated in previous studies; by inhibiting the proliferation of ECs, they induce the inhibitory effect of angiogenesis (7). The same effect has also been observed in melanoma and glioma, supporting the key role of FASN in the neovascularization of tumours (8,9).…”

Section: Fa Metabolism and Angiogenesissupporting

confidence: 74%

Roles of fatty acid metabolism in tumourigenesis: Beyond providing nutrition (Review)

Ren

Liang

et al. 2018

Mol Med Report

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Fatty acid (FA) metabolism, including the uptake, de novo synthesis and oxidation of FAs, is critical for the survival, proliferation, differentiation and metastasis of cancer cells. Several bodies of evidence have confirmed the metabolic reprogramming of FAs that occurs during cancer development. The present review aimed to evaluate FAs in terms of how the hallmarks of cancer are gradually established in tumourigenesis and tumour progression, and consider the auxo-action and exact mechanisms of FA metabolism in these processes. In addition, this interaction in the tumour microenvironment was also discussed. Based on the role of FA metabolism in tumour development, targeting FA metabolism may effectively target cancer, affecting a number of important characteristics of cancer progression and survival.

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Section: Fa Metabolism and Angiogenesissupporting

confidence: 74%

Roles of fatty acid metabolism in tumourigenesis: Beyond providing nutrition (Review)

Ren

Liang

et al. 2018

Mol Med Report

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“…Meanwhile, VEGFA was also found to be markedly upregulated in other tumours. The overexpression of VEGFA is a powerful predictor of overall survival and progression for some cancers, including breast cancer, prostate cancer, lung cancer and glioma [20][21][22][23][24]. Additionally, VEGFA was also demonstrated to increase the motility of PDAC cells [25].…”

Section: Introductionmentioning

confidence: 99%

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Zhao

Liu

et al. 2017

J Cellular Molecular Medi

117

126

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real‐time PCR. Corresponding adjacent non‐neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa‐miR29b‐3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up‐regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up‐regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa‐miR‐29b‐3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment.

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“…Lu et al considered that if FASN is a target gene of HIF, FASN levels would change with the change of HIF levels (33). However, Zhou et al reported inhibition of FASN blocked HIF-1α in glioma cells (32). In different tissues, the relationship of FASN and HIF-1α is different.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have reported that FASN inhibition regulates the expression of HIF-1α to various degrees in cancer cells (30)(31)(32). However, few studies have reported on the relationship of FASN and HIF-1α in HCC.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of FASN suppresses migration, invasion and growth in hepatoma carcinoma cells by deregulating the HIF-1α/IGFBP1 pathway

Gong

Shen

Yang

et al. 2017

International Journal of Oncology

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Hepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Due to a high propensity to metastasize, active angiogenesis and rapid proliferation, recurrence and poor prognosis are major obstacles for treatment and cure of this disease. However, the detailed mechanisms of how fatty acid synthase (FASN) promotes migration, invasion and healing in tumor cells remain unclear. In the present study, the previous results that FASN was expressed higher in cancer samples than in non-cancerous samples, and influenced migration, invasion of hepatoma carcinoma cells, were verified by immunohistochemistry, tissue microarrays, Transwell assay and wound healing assay. The secretory proteins of hepatocellular carcinoma cells with or without FASN knockdown were analyzed using the isobaric tags for relative and absolute quantitation (iTRAQ) method to identify differentially expressed proteins (DEPs). The DEPs were verified by RT-PCR and western blot analysis, and were consistent with the iTRAQ results. Inhibition of FASN can decrease the levels of IGFBP1, and the expression, activity, and ubiquitination of HIF-1α. Inhibition of FASN can suppress migration, invasion and healing of hepatoma carcinoma cells by decreasing HIF-1α, and IGFBP1.

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Inhibition of fatty acid synthase suppresses neovascularization via regulating the expression of VEGF-A in glioma

Abstract: Our results suggest that FASN plays a pivotal role in glioma neovascularization, and inhibition of FASN may be a potential target for anti-angiogenic therapy for glioma.

Cited by 25 publications

References 32 publications

Roles of fatty acid metabolism in tumourigenesis: Beyond providing nutrition (Review)

Roles of fatty acid metabolism in tumourigenesis: Beyond providing nutrition (Review)

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Inhibition of FASN suppresses migration, invasion and growth in hepatoma carcinoma cells by deregulating the HIF-1α/IGFBP1 pathway

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