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

Gong, Jiaojiao; Shen, Shasha; Yang, Yanwen; Qin, Si; Huang, Lingli; Zhang, Hongmin; Chen, Ling; Chen, Yaqin; Li, Shiying; She, Sha; Yang, Min; Ren, Hong; Hu, Huaidong

doi:10.3892/ijo.2017.3867

Cited by 29 publications

(23 citation statements)

References 41 publications

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“…Gong et al reported inhibition of FASN can suppress migration, invasion, and healing of hepatoma carcinoma cells by decreasing HIF-1α and IGFBP1 (ref. 42 ). However, our results suggest that it may not be enough to inhibit the lipid synthesis of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells

et al. 2020

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Metabolic interaction between cancer-associated fibroblasts (CAFs) and colorectal cancer (CRC) cells plays a major role in CRC progression. However, little is known about lipid alternations in CAFs and how these metabolic reprogramming affect CRC cells metastasis. Here, we uncover CAFs conditioned medium (CM) promote the migration of CRC cells compared with normal fibroblasts CM. CAFs undergo a lipidomic reprogramming, and accumulate more fatty acids and phospholipids. CAFs CM after protein deprivation still increase the CRC cells migration, which suggests small molecular metabolites in CAFs CM are responsible for CRC cells migration. Then, we confirm that CRC cells take up the lipids metabolites that are secreted from CAFs. Fatty acids synthase (FASN), a crucial enzyme in fatty acids synthesis, is significantly increased in CAFs. CAF-induced CRC cell migration is abolished by knockdown of FASN by siRNA or reducing the uptake of fatty acids by CRC cells by sulfo-N-succinimidyloleate sodium in vitro and CD36 monoclonal antibody in vivo. To conclude, our results provide a new insight into the mechanism of CRC metastasis and suggest FASN of CAFs or CD36 of CRC cells may be potential targets for anti-metastasis treatment in the future.

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Section: Discussionmentioning

confidence: 99%

Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells

et al. 2020

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“…Fatty acid synthase (FASN), which catalyzes the final step in fatty acid synthesis, is often overexpressed in human cancers ( 93 , 94 ). Inhibition of FASN suppresses invasion and migration of HCC cells ( 95 ). In contrast to enhanced fatty acid synthesis, certain types of cancer rely on the mitochondrial fatty acid oxidation (FAO) for ATP production ( 96 ).…”

Section: Lipid Metabolismmentioning

confidence: 99%

Dysregulated metabolic enzymes and metabolicï¿½reprogramming in cancer cells (Review)

Sreedhar

Zhao

2017

biom rep

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Tumor cells carry various genetic and metabolic alterations, which directly contribute to their growth and malignancy. Links between metabolism and cancer are multifaceted. Metabolic reprogramming, such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid (TCA) cycle metabolic enzymes, and dependence on lipid and glutamine metabolism are key characteristics of cancer cells. Understanding these metabolic alterations is crucial for development of novel anti-cancer therapeutic strategies. In the present review, the broad importance of metabolism in tumor biology is discussed, and the current knowledge on dysregulated metabolic enzymes involved in the vital regulatory steps of glycolysis, the TCA cycle, the pentose phosphate pathway, and lipid, amino acid, and mitochondrial metabolism pathways are reviewed.

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“…We previously observed that ursolic acid, a natural pentacyclic triterpenoid, and emodin, one anthraquinones constituents derivative isolated from the roots of rheum palmatuma, inhibited growth of hepatocellular carcinoma and lung cancer cells through induction of IGFBP1 gene expression, suggesting tumor suppressing role of this molecule [31, 32]. However, conflicting results were observed in other cancer types, such as prostate [33, 34] and endometrial cancer [35] and others [36]. Thus, IGFBP1 may play dual roles depending upon the environmental content, cells examined, and agents exposed.…”

Section: Introductionmentioning

confidence: 99%

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Tang

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE₂) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined. Methods: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western blot analysis and immunohistochemistry were performed to examine the phosphorylation and protein expressions of signal transducer and activator of transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1 were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and IGFBP1 were carried out by transient transfection assays. The promoter activity of IGFBP1 was tested using Secrete-Pair^TM Dual Luminescence Assay Kit. A xenografted tumor model was used to further test the effect of solamargine in combining with metformin in vivo. Results: We further demonstrated that solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell lines. Through mechanism-based approaches, we showed that solamargine decreased the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas reduced SP1 protein levels; all of which were abrogated in cells with overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and SP1. Moreover, solamargine increased mRNA, protein expression and promoter activity of IGFBP1, which was not observed in cells with overexpressed SP1 or with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA blocked the effect of solamargine on cell growth inhibition. More importantly, there was a synergy of combination of solamargine and metformin. Similar findings were also observed in vivo. Conclusion: Our results show that solamargine increases IGFBP1 gene expression through inactivation of Stat3, followed by regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo. This ultimately leads to suppression of human lung cancer cell growth. Moreover, this is a synergy of solamargine in combination with metformin in this process. This study unravels a novel mechanism underlying the anti-lung cancer effects of solamargine in combination of metformin, and suggests a potential new lung cancer associated therapy.

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

Cited by 29 publications

References 41 publications

Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells

Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells

Dysregulated metabolic enzymes and metabolicï¿½reprogramming in cancer cells (Review)

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

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