Blocking fatty acid synthase inhibits tumor progression of human osteosarcoma by regulating the human epidermal growth factor receptor 2/phosphoinositide 3-kinase/protein kinase B signaling pathway in xenograft models

Chen, Xuan Yin; Ruan, Hui; Long, Xin; Peng, Ai; Zhou, Long; Liu, Jia Ming; Zhou, Yang; Liu, Zhi Li

doi:10.3892/etm.2017.4284

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…Previous experimental evidence has suggested that fatty acid synthase (FASN) may be involved in cancer metastasis, and have been investigated as a therapeutic target ( 40 , 41 ). The role of FASN in progression and metastasis development in osteosarcoma was demonstrated in previous studies ( 42 ). In our study, the expression of FASN was significantly higher in metastatic cases and in patients who died, than those without metastasis and who survived, showing similar results to previous studies ( 43 ).…”

Section: Discussionsupporting

confidence: 53%

In Situ Analysis of mTORC1/C2 and Metabolism-Related Proteins in Pediatric Osteosarcoma

Mohas

Krencz

Váradi

et al. 2022

Pathol. Oncol. Res.

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Activation of the mTOR pathway has been observed in osteosarcoma, however the inhibition of mammalian target of rapamycin (mTOR) complex 1 has had limited results in osteosarcoma treatment. Certain metabolic pathways can be altered by mTOR activation, which can affect survival. Our aim was to characterize the mTOR profile and certain metabolic alterations in pediatric osteosarcoma to determine the interactions between the mTOR pathway and metabolic pathways. We performed immunohistochemistry on 28 samples to analyze the expression of mTOR complexes such as phospho-mTOR (pmTOR), phosphorylated ribosomal S6 (pS6), and rapamycin-insensitive companion of mTOR (rictor). To characterize metabolic pathway markers, we investigated the expression of phosphofructokinase (PFK), lactate dehydrogenase-A (LDHA), β-F1-ATPase (ATPB), glucose-6-phosphate dehydrogenase (G6PDH), glutaminase (GLS), fatty acid synthetase (FASN), and carnitin-O-palmitoyltransferase-1 (CPT1A). In total, 61% of the cases showed low mTOR activity, but higher pmTOR expression was associated with poor histological response to chemotherapy and osteoblastic subtype. Rictor expression was higher in metastatic disease and older age at the time of diagnosis. Our findings suggest the importance of the Warburg-effect, pentose-phosphate pathway, glutamine demand, and fatty-acid beta oxidation in osteosarcoma cells. mTOR activation is linked to several metabolic pathways. We suggest performing a detailed investigation of the mTOR profile before considering mTORC1 inhibitor therapy. Our findings highlight that targeting certain metabolic pathways could be an alternative therapeutic approach.

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Section: Discussionsupporting

confidence: 53%

In Situ Analysis of mTORC1/C2 and Metabolism-Related Proteins in Pediatric Osteosarcoma

Mohas

Krencz

Váradi

et al. 2022

Pathol. Oncol. Res.

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“…[101][102][103][104] Some studies have found that FASN inhibition inhibited OS metastasis by downregulating the HER2/PI3K/AKT signaling pathway. 105,106 Yet other studies found by PI3K/AKT signaling pathway to affect FASN expression. 104,107…”

Section: Fatty Acid Synthesis Pathwaymentioning

confidence: 93%

“…Several studies have found that miRNA‐424, miRNA‐195, α ‐linolenic acid, and lapatinib can inhibit FASN to reduce the malignant phenotype of OS 101–104 . Some studies have found that FASN inhibition inhibited OS metastasis by downregulating the HER2/PI3K/AKT signaling pathway 105,106 . Yet other studies found by PI3K/AKT signaling pathway to affect FASN expression 104,107 …”

Section: Lipid Synthesis In Osteosarcomamentioning

confidence: 99%

Metabolic reprogramming in osteosarcoma

Shi

Yue

Luo

2023

Pediatric Discovery

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Tumor cells undergo metabolic reprogramming to meet their energy and anabolic demands to maintain their malignant phenotype. Activation of oncogenes and deletion of tumor suppressors promotes metabolic reprogramming in cancer by directly or indirectly regulating enzymatic activities associated with metabolic pathways. Metabolic reprogramming in tumor cells mainly involves the glycolytic pathway, pentose phosphate pathway, serine synthesis pathway, enhanced glutamine metabolism or fatty acid anabolism, and abnormal mitochondrial oxidative phosphorylation (OXPHOS). The tricarboxylic acid (TCA) cycle is the central pathway of mitochondrial OXPHOS, and glucose, amino acid and fatty acid metabolism are associated with the TCA cycle. Metabolic abnormalities and rewiring of metabolic pathways are also present in Osteosarcoma (OS). The abnormal metabolic pattern in OS is associated with cell proliferation, migration, invasion and drug resistance. This review summarizes the current studies on glycolysis, amino acid metabolism, lipid synthesis and the TCA cycle related to OS.

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“…FASN is expressed at high levels in a variety of human tumors such as prostate cancer 7 . In fact, FASN has been studied as a candidate oncogene in cancer 8 such as prostate cancer 9 , liver cancer 10 , and ovarian cancer 11 . Recently evidences showed that fatty acid metabolic pathways played a critical role in carcinogenesis 12 .…”

Section: Introductionmentioning

confidence: 99%

Anoikis resistant mediated by FASN promoted growth and metastasis of osteosarcoma

et al. 2019

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The pulmonary metastasis of osteosarcoma (OS) occurs commonly, which resulted from anoikis resistant (AR) of tumor cells as reported by previous studies, but the exact roles of AR in osteosarcoma were not fully studied. Our previous investigations showed fatty acid synthase (FASN) was relating to clinical features of patients with OS. In this study, we aim to explore the functions of FASN in the AR OS cells in vitro and in vivo and study the downstream effectors of FASN. In the present study, we used our established cell model to study the AR. We revealed that AR promoted cell proliferation and migration as determined by colony formation assay and transwell assay. In addition, AR assisted tumor growth in vivo. In the AR cells, the expression of FASN was higher. Thus, we constructed lentiviruses to silence or overexpress FASN in four cell lines to study functions of FASN. Silence of FASN reduced cell colonies and migration while overexpression of FASN increased colonies and migration in suspended cells. Loss of functions of FASN induced cell apoptosis in suspended OS cells while gain of function of FASN suppressed apoptosis as determined by flow cytometry. We found the levels of p-ERK1/2 and Bcl-xL declined when FASN was silenced while they increased when FASN was overexpressed. In addition, results showed that the levels of FASN and its potential related molecules (p-ERK1/2 and Bcl-xL) increased in 143B-AR and MG-63-AR cells. In vivo study showed that inhibition of FASN decreased pulmonary metastasis of OS. In conclusion, we showed that anoikis resistant and FASN as two interactional factors facilitated the progress of osteosarcoma.

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Blocking fatty acid synthase inhibits tumor progression of human osteosarcoma by regulating the human epidermal growth factor receptor 2/phosphoinositide 3-kinase/protein kinase B signaling pathway in xenograft models

Cited by 5 publications

References 38 publications

In Situ Analysis of mTORC1/C2 and Metabolism-Related Proteins in Pediatric Osteosarcoma

In Situ Analysis of mTORC1/C2 and Metabolism-Related Proteins in Pediatric Osteosarcoma

Metabolic reprogramming in osteosarcoma

Anoikis resistant mediated by FASN promoted growth and metastasis of osteosarcoma

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