TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

Wang, Hua; Dijke, Peter ten; Kostidis, Sarantos; Giera, Martin; Hornsveld, Marten

doi:10.1007/s00018-019-03398-6

Cited by 183 publications

(169 citation statements)

References 186 publications

(224 reference statements)

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“…In summary, our study allowed us to conclude that 21 pathways had similar differences in all three cell lines after induction of EMT ( Figure 1B and Supplementary Tables 1-3). We identified some pathways related to amino acids metabolism, such as alanine, glycine, serine, and glutamate, among others, according to other studies (11,15,17,18). Furthermore, we discovered that additional pathways such as Fatty Acid metabolism, Citric Acid Cycle, and glutathione metabolism also changed after EMT (Supplementary Table 13).…”

Section: Different Nsclc Cell Lines Have Similarities In Metabolic Rementioning

confidence: 88%

Analysis of Epithelial-Mesenchymal Transition Metabolism Identifies Possible Cancer Biomarkers Useful in Diverse Genetic Backgrounds

Matadamas-Guzman

Zazueta

Rojas³

et al. 2020

Front. Oncol.

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Epithelial-to-mesenchymal transition (EMT) relates to many molecular and cellular alterations that occur when epithelial cells undergo a switch in differentiation generating mesenchymal-like cells with newly acquired migratory and invasive properties. In cancer cells, EMT leads to drug resistance and metastasis. Moreover, differences in genetic backgrounds, even between patients with the same type of cancer, also determine resistance to some treatments. Metabolic rewiring is essential to induce EMT, hence it is important to identify key metabolic elements for this process, which can be later used to treat cancer cells with different genetic backgrounds. Here we used a mathematical modeling approach to determine which are the metabolic reactions altered after induction of EMT, based on metabolomic and transcriptional data of three non-small cell lung cancer (NSCLC) cell lines. The model suggested that the most affected pathways were the Krebs cycle, amino acid metabolism, and glutathione metabolism. However, glutathione metabolism had many alterations either on the metabolic reactions or at the transcriptional level in the three cell lines. We identified Glutamate-cysteine ligase (GCL), a key enzyme of glutathione synthesis, as an important common feature that is dysregulated after EMT. Analyzing survival data of men with lung cancer, we observed that patients with mutations in GCL catalytic subunit (GCLC) or Glutathione peroxidase 1 (GPX1) genes survived less time than people without mutations on these genes. Besides, patients with low expression of ANPEP, GPX3 and GLS genes also survived less time than those with high expression. Hence, we propose that glutathione metabolism and glutathione itself could be good targets to delay or potentially prevent EMT induction in NSCLC cell lines.

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Section: Different Nsclc Cell Lines Have Similarities In Metabolic Rementioning

confidence: 88%

Analysis of Epithelial-Mesenchymal Transition Metabolism Identifies Possible Cancer Biomarkers Useful in Diverse Genetic Backgrounds

Matadamas-Guzman

Zazueta

Rojas³

et al. 2020

Front. Oncol.

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“…This result was consistent with our research, suggesting that the EMT process could act as an important regulator during the progression of NSCLC. Since it has been reported that TGF-β signaling could be involved in the EMT process of malignant tumors [41], we will further Figure 5: MiR-188-3p directly targeted NCAPG2. (a) Gene structure of NCAPG2 at the position of 123-130 indicated the predicted target site of miR-188-3p in its 3′UTR, with a sequence of CCCAA.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA FGF12-AS2 suppresses the tumorigenesis of NSCLC via sponging miR-188-3p

et al. 2020

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BackgroundNon-small-cell lung carcinoma (NSCLC) seriously threatens the health of human beings. Aberrant expression of lncRNAs has been confirmed to be related with the progression of multiple malignant tumors, including NSCLC. LncRNA FGF12-AS2 has been considered to be upregulated in NSCLC. However, the mechanism by which FGF12-AS2 promotes the tumorigenesis of NSCLC remains elusive.MethodsGene and protein expressions in NSCLC cells were measured by q-PCR and western blot, respectively. CCK-8 and immunofluorescence staining were performed to detect the cell proliferation. Cell apoptosis was tested by flow cytometry. Transwell assay was used to detect the cell migration and invasion. Finally, the dual luciferase report assay was used to verify the relation among FGF12-AS2, miR-188-3p, and NCAPG2.ResultsDownregulation of FGF12-AS2 significantly inhibited the proliferation of NSCLC cells via inducing apoptosis. In addition, FGF12-AS2 silencing notably suppressed the migration and invasion of A549 cells. Meanwhile, FGF12-AS2 modulated the progression of NSCLC via regulation of miR-188-3p/NCAPG2 axis. Finally, knockdown of FGF12-AS2 inhibited the tumorigenesis of NSCLC via suppressing the EMT process of NSCLC.ConclusionDownregulation of lncRNA FGF12-AS2 suppressed the tumorigenesis of NSCLC via sponging miR-188-3p. Thus, FGF12-AS2 may serve as a potential target for the treatment of NSCLC.

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“…Emerging evidence has proven that TGF-β signaling possesses both Smad and non-Smad pathways, and regulated tumorigenesis via different molecular mechanisms, including, TGF-β1/Smad2/3, PI3K-AKT-mTOR, Wnt, Notch, and ERK, p38, and JUN N-terminal kinase (JNK) MAPK pathways [34][35]. Various studies also indicated that TGF-β was signi cantly associated with the expression of MAGs and metabolic reprogramming of cancer [36][37][38]. Therefore, M2 TAMs secreted TGF-β1 may in uence the metabolic reprogramming in BC by these signaling pathways, especially Smad pathways, to promote the recurrence and progression of BC.…”

Section: Discussionmentioning

confidence: 99%

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

Shen

Liu

Wang

et al. 2020

Preprint

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Background: Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data. Methods: RNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) was further perform to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells.Results: A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAM secreted TGF-β1 in T24 cells.Conclusions: Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental exploration are needed to validate our observations in BC.

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TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

Cited by 183 publications

References 186 publications

Analysis of Epithelial-Mesenchymal Transition Metabolism Identifies Possible Cancer Biomarkers Useful in Diverse Genetic Backgrounds

Analysis of Epithelial-Mesenchymal Transition Metabolism Identifies Possible Cancer Biomarkers Useful in Diverse Genetic Backgrounds

Downregulation of lncRNA FGF12-AS2 suppresses the tumorigenesis of NSCLC via sponging miR-188-3p

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

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