Anlotinib suppresses lung adenocarcinoma growth via inhibiting FASN-mediated lipid metabolism

Shen, Juan; Huang, Jie; Huang, Yu; Chen, Yidan; Li, Jiawei; Luo, Peihua; Zhang, Qianyun; Qiu, Yao; Wang, Lie; Jiang, Hong; Ma, Shenglin; Chen, Xueqin

doi:10.21037/atm-22-5438

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Targeting lipid metabolism has become an attractive choice for cancer treatment [ 30 ]. Emerging evidence has determined that many molecules exhibit therapeutic potential against LUAD through inhibiting lipid metabolism, such as Anlotinib (a vascular endothelial growth factor receptor inhibitor) [ 31 ] and endothelial lipase gene [ 32 ]. To combine with our findings, we speculated that the inhibition of lipid metabolism may contribute to the role of CD147 silencing in inhibiting LUAD.…”

Section: Discussionmentioning

confidence: 99%

Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway

Zhang,

Liu,

Lai

et al. 2023

Respir Res

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Objective CD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms. Methods Followed by silencing of CD147, the viability, migration, invasion, and apoptosis of LUAD cells were measured by CCK8, wound healing, transwell assay, and flow cytometer, respectively. The expression of CD147 and two markers of lipid metabolism (FASN and ACOX1) were detected by qRT-PCR. A xenograft tumor model was constructed to investigate the function of CD147 in vivo. Then transcriptome sequencing was performed to explore the potential mechanisms. After measuring the expression of Rap1 and p-p38 MAPK/p38 MAPK by western blot, the changes of CD147 and lipid metabolism markers (FASN, ACOX1) was detected by Immunohistochemistry. Moreover, a Rap1 activator and a Rap1 inhibitor were applied for feedback functional experiments. Results CD147 was up-regulated in LUAD cells, and its silencing inhibited cell proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis, while overexpression of CD147 showed the opposite results. Silencing of CD147 also inhibited the growth of tumor xenografts in mice. Transcriptome sequencing revealed 834 up-regulated differentially expressed genes (DEGs) and 602 down-regulated DEGs. After functional enrichment, the Rap1 signaling pathway was selected as a potential target, which was then verified to be blocked by CD147 silencing. In addition, the treatment of Rap1 activator weakened the inhibiting effects of si-CD147 on the proliferation, migration, invasion, and lipid metabolism in LUAD cells, while the intervention of RAP1 inhibitor showed the opposite results. Conclusions Silencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway

Zhang,

Liu,

Lai

et al. 2023

Respir Res

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“…Related drugs could act on the FAM process in LUAD. For example, anlotinib controls LUAD progression through inhibiting FASN-mediated FAM ( Shen et al, 2022 ). Chaoyang Liang et al also showed that the overexpression of genes related to FAM enzymes (ACOT11) regulates the growth, differentiation, and metastasis of LUAD cells through a variety of signaling pathways ( Liang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Applying machine learning algorithms to develop a survival prediction model for lung adenocarcinoma based on genes related to fatty acid metabolism

Cong,

Zhao,

Zhang

et al. 2023

Front. Pharmacol.

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Background: The progression of lung adenocarcinoma (LUAD) may be related to abnormal fatty acid metabolism (FAM). The present study investigated the relationship between FAM-related genes and LUAD prognosis.Methods: LUAD samples from The Cancer Genome Atlas were collected. The scores of FAM-associated pathways from the Kyoto Encyclopedia of Genes and Genomes website were calculated using the single sample gene set enrichment analysis. ConsensusClusterPlus and cumulative distribution function were used to classify molecular subtypes for LUAD. Key genes were obtained using limma package, Cox regression analysis, and six machine learning algorithms (GBM, LASSO, XGBoost, SVM, random forest, and decision trees), and a RiskScore model was established. According to the RiskScore model and clinical features, a nomogram was developed and evaluated for its prediction performance using a calibration curve. Differences in immune abnormalities among patients with different subtypes and RiskScores were analyzed by the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data, CIBERSORT, and single sample gene set enrichment analysis. Patients’ drug sensitivity was predicted by the pRRophetic package in R language.Results: LUAD samples had lower scores of FAM-related pathways. Three molecular subtypes (C1, C2, and C3) were defined. Analysis on differential prognosis showed that the C1 subtype had the most favorable prognosis, followed by the C2 subtype, and the C3 subtype had the worst prognosis. The C3 subtype had lower immune infiltration. A total of 12 key genes (SLC2A1, PKP2, FAM83A, TCN1, MS4A1, CLIC6, UBE2S, RRM2, CDC45, IGF2BP1, ANGPTL4, and CD109) were screened and used to develop a RiskScore model. Survival chance of patients in the high-RiskScore group was significantly lower. The low-RiskScore group showed higher immune score and higher expression of most immune checkpoint genes. Patients with a high RiskScore were more likely to benefit from the six anticancer drugs we screened in this study.Conclusion: We developed a RiskScore model using FAM-related genes to help predict LUAD prognosis and develop new targeted drugs.

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The role of ESM1 in the lipids metabolic reprogramming and angiogenesis of lung adenocarcinoma cells

Feng,

Ting,

Tang

et al. 2024

Heliyon

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Anlotinib suppresses lung adenocarcinoma growth via inhibiting FASN-mediated lipid metabolism

Cited by 3 publications

References 41 publications

Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway

Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway

Applying machine learning algorithms to develop a survival prediction model for lung adenocarcinoma based on genes related to fatty acid metabolism

The role of ESM1 in the lipids metabolic reprogramming and angiogenesis of lung adenocarcinoma cells

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