Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation

Coleman, David T.; Bigelow, Rebecca L.; Cardelli, James A.

doi:10.1158/1535-7163.mct-08-0722

Cited by 61 publications

(66 citation statements)

References 42 publications

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“…FASN is expressed at high levels in a variety of human tumors (11)(12)(13)(14), but exists at low levels in normal tissues. Various studies have reported that the inhibition of FASN expression suppresses cancer cell proliferation in vitro and in vivo (15)(16)(17)(18)(19)(20). Thus, FASN is considered a novel promising target for anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN

et al. 2012

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Abstract. microRNAs are involved in different cancer-related processes. miR-195, one of the miR-16/15/195/424/497 family members, has been shown to act as a tumor suppressor during tumorigenesis. However, the function of miR-195 in osteosarcoma is still unclear. In our study, the miR-195 expression level was upregulated in osteosarcoma cells, by transfection with miR-195, and the fatty acid synthase (FASN) mRNA and protein expression levels were measured by RT-PCR and western blotting. Cell migration and invasion was measured using wound healing migration and Transwell invasion assays. We found that the upregulation of miR-195 greatly decreased cell invasion and the migration of U2OS. We also identified that FASN may be a direct target of miR-195 by the luciferase activity assay. These findings provide evidence that miR-195 plays a key role in inhibiting osteosarcoma cell migration and invasion through targeting FASN, and strongly suggest that exogenous miR-195 may have therapeutic value in treating osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN

et al. 2012

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“…This overexpression in neoplastic tissues makes FASN a potential diagnostic tumor marker. The inhibition of FASN activity is selectively cytotoxic to human cancer cells in vitro and in vivo (17,18). Thus, FASN is considered a novel and promising target for antineoplastic therapy.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid synthase expression in osteosarcoma and its correlation with pulmonary metastasis

et al. 2012

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Abstract. Previous experimental evidence has suggested that fatty acid synthase (FASN) may be involved in cancer metastasis. However, its role has been poorly evaluated in osteosarcoma. The aim of this study was to investigate the correlation of FASN expression with pulmonary metastasis and the correlation of FASN expression with the Ki-67 antigen, a proliferation marker, in patients with osteosarcoma of the extremities. The expression of FASN protein and Ki-67 was detected by immunohistochemistry of biopsy tissues from 136 patients with osteosarcoma of the extremities and 21 cases of osteoenchondroma. Positive expression of the FASN protein was observed and located in the cytoplasm. The positive expression rate of FASN was 63.2% in osteosarcoma and 28.6% in osteoenchondroma (p<0.05). The expression levels of the FASN protein were higher in the cases with lung metastasis compared to those without metastasis (p<0.01). The percentage of Ki-67 stained nuclei in osteosarcoma with pulmonary metastasis and in those without was 43.43±10.05 and 25.41±6.68%, respectively (p<0.01). There was a positive correlation between FASN and Ki-67 protein expression in osteosarcoma (Spearman's rho, F=43.05, R=0.734). Therefore, FASN may be a promising target in the treatment of osteosarcoma metastasis.

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“…Recent studies have suggested that there is a functional interaction between FASN enzymatic activity and different receptor tyrosine kinases (RTK) such as HER2 and c-Met (14,15). RTKs and their specific ligands are essential components of intracellular signaling pathways used for the control of growth, differentiation, and survival.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Fatty Acid Synthase Suppresses c-Met Receptor Kinase and Induces Apoptosis in Diffuse Large B-Cell Lymphoma

Uddin

Hussain

Ahmed

et al. 2010

Molecular Cancer Therapeutics

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Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers; however, its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. In this study, we investigated the role of FASN in a large series of DLBCL tissues in a tissue microarray (TMA) format followed by in vitro studies using DLBCL cell lines. FASN was found to be expressed in 62.6% DLBCL samples and was seen in highly proliferative tumors, manifested by high Ki67 (P < 0.0001). Significant association was found between tumors expressing high FASN and c-Met tyrosine kinase (P < 0.0002), as well as p-AKT (P = 0.0309). In vitro, pharmacological FASN inhibition and small interference RNA (siRNA) targeted against FASN triggered caspase-dependent apoptosis and suppressed expression of c-Met kinase in DLBCL cell lines, which further highlighted the molecular link between FASN and c-Met kinase. Finally, simultaneous targeting of FASN and c-Met with specific chemical inhibitors induced a synergistically stimulated apoptotic response in DLBCL cell lines. These findings provide evidence that FASN, via c-Met tyrosine kinase, plays a critical role in the carcinogenesis of DLBCL and strongly suggest that targeting FASN may have therapeutic value in treatment of DLBCL. Mol Cancer Ther; 9(5); 1244-55. ©2010 AACR.

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Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation

Cited by 61 publications

References 42 publications

microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN

microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN

Fatty acid synthase expression in osteosarcoma and its correlation with pulmonary metastasis

Inhibition of Fatty Acid Synthase Suppresses c-Met Receptor Kinase and Induces Apoptosis in Diffuse Large B-Cell Lymphoma

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