Obesity promotes gastric cancer metastasis via diacylglycerol acyltransferase 2-dependent lipid droplets accumulation and redox homeostasis

Li, Shuai; Wu, Teng; Lu, Yong; Wang, Jinxiang; Yu, Feng-Hai; Yang, Meizhu; Huang, Yijia; Li, Zhi-Jing; Wang, Sen-Lan; Huang, Ling; Lü, Lei; Tian, Tian

doi:10.1016/j.redox.2020.101596

Cited by 51 publications

(50 citation statements)

References 42 publications

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“…Secreted factor induced by oxidative stress in adipocytes are involved in the reduction of oxidative stress induced by daunorubicin and by radiation in leukaemia cells [18]. In gastric cancer cells, adipocyte proximity decreases oxidative stress induced by cell detachment through increase in NAPDH production and glutathione leading to anoikis resistance and metastasis in mice [86].…”

Section: I) Metabolic Rolesmentioning

confidence: 99%

Interaction between adipose tissue and cancer cells: role for cancer progression

Dumas

Brisson

2020

Cancer Metastasis Rev

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Environment surrounding tumours are now recognised to play an important role in tumour development and progression. Among the cells found in the tumour environment, adipocytes from adipose tissue establish a vicious cycle with cancer cells to promote cancer survival, proliferation, metastasis and treatment resistance. This cycle is particularly of interest in the context of obesity which has been found as cancer risk factor. Cancers cells can reprogram adipocyte physiology leading to an "activated" phenotype characterized by delipidation and secretion of inflammatory adipokines. The adipocyte secretions then influence tumour growth and metastasis which has been mainly attributed to interleukin 6 (IL-6) or leptin but also to the release of fatty acids which are able to change cancer cell metabolism and signalling pathways.The aim of this review is to report recent advances in the understanding of the molecular mechanisms linking adipose tissue with cancer progression in order to propose new therapeutic strategies based on pharmacological or nutritional intervention.

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Section: I) Metabolic Rolesmentioning

confidence: 99%

Interaction between adipose tissue and cancer cells: role for cancer progression

Dumas

Brisson

2020

Cancer Metastasis Rev

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“…The levels of Brf1 immunostaining were evaluated independently by two pathologists who were blinded to the survival outcomes of the participants based on the proportion of positively stained tumor cells (stain area) and the intensity of staining [ 20 ]. The immunostaining results were performed by multiplying the staining intensity by the stained area (staining index (SI)) as previously described [ 30 , 36 , 37 ]. The Brf1 expression levels in lung cancer lesions were determined by the SI, which was 0, 1, 2, 3, 4, 6, 9, or 12.…”

Section: Methodsmentioning

confidence: 99%

“…The Brf1 expression levels in lung cancer lesions were determined by the SI, which was 0, 1, 2, 3, 4, 6, 9, or 12. An optimal cutoff value was identified as follows: an SI score of ≥6 was used to define tumors as high Brf1 expression, and an SI score of ≤4 as low [ 30 , 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

“…Transfections were performed using Lipofectamine 3000 and OPTI-MEM reagent (Life Technologies, Cat No. L3000015 and 11058021) when cells were approximately 40% confluent and transfected according to the manufacturer's instruction [ 37 ]. For Brf1-Luc promoter activity, cells were transfected with 0.5 μ g of the Brf1-Luc report constructs for 48 h. Cells were starved in FBS-free RPMI 1640 for 4 h and treated with different concentrations of MNNG for another 2 h. Cell pellets were dissolved in Promega reporter lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

“…We carried out statistical analysis with Student's t -test, ANOVA and Tukey's multiple comparisons test, Kaplan-Meier and log-rank test, ROC curve, and Cox analysis. The details of the statistical analysis were described previously [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

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Exploring the Role and Mechanism of pAMPKα‐Mediated Dysregulation of Brf1 and RNA Pol III Genes

Zhang

Lin

et al. 2021

Oxidative Medicine and Cellular Longevity

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TF IIB-related factor 1 (Brf1) is a key transcription factor of RNA polymerase III (Pol III) genes. Our early studies have demonstrated that Brf1 and Pol III genes are epigenetically modulated by histone H3 phosphorylation. Here, we have further investigated the relationship of the abnormal expression of Brf1 with a high level of phosphorylated AMPKα (pAMPKα) and explored the role and molecular mechanism of pAMPKα-mediated dysregulation of Brf1 and Pol III genes in lung cancer. Brf1 is significantly overexpressed in lung cancer cases. The cases with high Brf1 expression display short overall survival times. Elevation of Brf1 expression is accompanied by a high level of pAMPKα. Brf1 and pAMPKα colocalize in nuclei. Further analysis indicates that the carcinogen MNNG induces pAMPKα to upregulate Brf1 expression, resulting in the enhancement of Pol III transcription. In contrast, inhibiting pAMPKα decreases cellular levels of Brf1, resulting in the reduction of Pol III gene transcription to attenuate the rates of cell proliferation and colony formation of lung cancer cells. These outcomes demonstrate that high Brf1 expression reveals a worse prognosis in lung cancer patients. pAMPKα-mediated dysregulation of Brf1 and Pol III genes plays important roles in cell proliferation, colony formation, and tumor development of lung cancer. Brf1 may be a biomarker for establishing the prognosis of lung cancer. It is a new mechanism that pAMPKα mediates dysregulation of Brf1 and Pol III genes to promote lung cancer development.

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A Mammalian Conserved Circular RNA CircLARP1B Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism

Li,

Wang,

Shi

et al. 2023

Advanced Science

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Circular RNAs (circRNAs) have emerged as crucial regulators in physiology and human diseases. However, evolutionarily conserved circRNAs with potent functions in cancers are rarely reported. In this study, a mammalian conserved circRNA circLARP1B is identified to play critical roles in hepatocellular carcinoma (HCC). Patients with high circLARP1B levels have advanced prognostic stage and poor overall survival. CircLARP1B facilitates cellular metastatic properties and lipid accumulation through promoting fatty acid synthesis in HCC. CircLARP1B deficient mice exhibit reduced metastasis and less lipid accumulation in an induced HCC model. Multiple lines of evidence demonstrate that circLARP1B binds to heterogeneous nuclear ribonucleoprotein D (HNRNPD) in the cytoplasm, and thus affects the binding of HNRNPD to sensitive transcripts including liver kinase B1 (LKB1) mRNA. This regulation causes decreased LKB1 mRNA stability and lower LKB1 protein levels. Antisense oligodeoxynucleotide complementary to theHNRNPD binding sites in circLARP1B increases the HNRNPD binding to LKB1 mRNA. Through the HNRNPD–LKB1–AMPK pathway, circLARP1B promotes HCC metastasis and lipid accumulation. Results from AAV8‐mediated hepatocyte‐directed knockdown of circLARP1B or Lkb1 in mouse models also demonstrate critical roles of hepatocytic circLARP1B regulatory pathway in HCC metastasis and lipid accumulation, and indicate that circLARP1B may be potential target of HCC treatment.

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Obesity promotes gastric cancer metastasis via diacylglycerol acyltransferase 2-dependent lipid droplets accumulation and redox homeostasis

Cited by 51 publications

References 42 publications

Interaction between adipose tissue and cancer cells: role for cancer progression

Interaction between adipose tissue and cancer cells: role for cancer progression

Exploring the Role and Mechanism of pAMPKα‐Mediated Dysregulation of Brf1 and RNA Pol III Genes

A Mammalian Conserved Circular RNA CircLARP1B Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism

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