The aberrant cancer metabolic gene carbohydrate sulfotransferase 11 promotes non-small cell lung cancer cell metastasis via dysregulation of ceruloplasmin and intracellular iron balance

Chang, Wei‐Min; Li, Lijie; Chiu, I-An; Lai, Tsung‐Ching; Chang, Yu‐Chan; Tsai, Henry J.; Yang, Chih‐Jen; Huang, Ming-Shyan; Su, Cheng-Tau; Lai, Ting-Lun; Jan, Yi-Hua; Hsiao, Michael

doi:10.1016/j.tranon.2022.101508

Cited by 10 publications

(11 citation statements)

References 44 publications

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“…Several positively and negatively associated metabolic processes with EMT were identified which were found concordant in multiple profiles of lung cancer performed using microarray or RNA-Seq technique showing that the pathway-centric analysis carried out here is technologically independent. Previously reported EMT-associated metabolic processes were also found to have both positive (chondriotin sulphate [39], heparan sulphate [40]), and negative (TCA, oxidative phosphorylation, and fatty acid synthesis [56]) connections in the current study. While short-chain fatty acids, propionate and butyrate, were the most negatively associated metabolic processes with EMT, several unreported roles of glycosaminoglycans such as dermatan sulphate or vitamin B5 metabolic processes were not explored deeply in the literature, and requires further investigation in the context of EMT in cancer.…”

Section: Discussionsupporting

confidence: 70%

“…With a stringent cut-off of clinically accepted meta-correlation (r<-0.3 and r>0.3), we identified several previously reported positively and negatively associated processes with EMT ( Figure 1A , Supplementary Figure 2 and Supplementary Table 3-4 ). For instance, we observed chondroitin sulphate biosynthesis [39] or heparan biosynthesis [40] to have positive association with EMT gene signature including TGF signaling, ECM receptors interaction, and gap junction degradation. Interestingly, we found EMT to have negative associations with the short-chain fatty acids (SCFAs), propionate (meta r = −0.46; meta p-value<0.0001) and butanoate (meta r = −0.46; meta p-value<0.0001) metabolic processes ( Figure 1B-D ; Supplementary Table 3 ), which have not been investigated in detail previously in the context of lung cancer mediated EMT process.…”

Section: Resultsmentioning

confidence: 99%

Section: Short-chain Fatty Acids Show Negative Association With Emt I...mentioning

confidence: 99%

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Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

Ramesh

Gollavilli

Pinna

et al. 2023

Preprint

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Epithelial to mesenchymal transition (EMT) is a developmental cellular program driving metastasis and chemo-resistance in cancer, but its pharmacological treatment has been so far challenging. Targeting deregulated metabolic processes in cancer is emerging as a realistic therapeutic strategy. Here, we used an EMT-focussed integrative functional genomic approach and identified negative association of the short-chain fatty acids, propionate and butanoate, with EMT in non-small cell lung cancer (NSCLC) patients. Strikingly, in vitro treatment of lung cancer cell lines with propionate reinforced the epithelial transcriptional program promoting cell adhesion, and reverting the aggressive and chemoresistant EMT phenotype. Propionate treatment reduced cells metastatic ability in nude mice and limited lymph nodal spread in a genetic NSCLC mouse model. Further, analyses indicated chromatin remodeling via H3K27 acetylation (p300-mediated) as the mechanism shifting the EMT balance towards epithelial state upon propionate. Propionate administration could be tested in the clinic for reducing NSCLC aggressiveness.

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Section: Discussionsupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Short-chain Fatty Acids Show Negative Association With Emt I...mentioning

confidence: 99%

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Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

Ramesh

Gollavilli

Pinna

et al. 2023

Preprint

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“…Third, pan‐cancer EMT gene signature and metabolic process gene‐sets activation pattern in lung cancer gene expression profiles was computed using z ‐score based approach. Finally, an EMT‐centered investigation, with a clinically accepted meta‐correlation (meta‐ r < −0.3 and meta‐ r > 0.3; meta‐ P value < 0.05), has identified several positively and negatively associated metabolic processes (Fig 1A, Appendix Tables S4 and S5) including previously reported chondroitin sulphate (Chang et al , 2022) and heparan (Zhang et al , 2018) biosynthetic processes. Interestingly, EMT was found negatively correlated with short‐chain fatty acids (SCFAs), propionate (meta‐ r = −0.46) and butanoate (meta‐ r = −0.46) (Appendix Table S4) which have not been investigated in detail previously in the context of lung cancer mediated EMT process.…”

Section: Resultsmentioning

confidence: 89%

Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma

Ramesh,

Gollavilli,

Pinna

et al. 2023

EMBO Mol Med

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The epithelial‐to‐mesenchymal transition (EMT) plays a central role in the development of cancer metastasis and resistance to chemotherapy. However, its pharmacological treatment remains challenging. Here, we used an EMT‐focused integrative functional genomic approach and identified an inverse association between short‐chain fatty acids (propionate and butanoate) and EMT in non‐small cell lung cancer (NSCLC) patients. Remarkably, treatment with propionate in vitro reinforced the epithelial transcriptional program promoting cell‐to‐cell contact and cell adhesion, while reducing the aggressive and chemo‐resistant EMT phenotype in lung cancer cell lines. Propionate treatment also decreased the metastatic potential and limited lymph node spread in both nude mice and a genetic NSCLC mouse model. Further analysis revealed that chromatin remodeling through H3K27 acetylation (mediated by p300) is the mechanism underlying the shift toward an epithelial state upon propionate treatment. The results suggest that propionate administration has therapeutic potential in reducing NSCLC aggressiveness and warrants further clinical testing.

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“…The elevated expression of CHST11 in patients with lung cancer and pancreatic cancer is correlated with poor prognosis 5 , 6 . The aberrant expression of CHST11 facilitates the proliferation, migration, and invasion of tumor cells and promotes the emergence of biological behavior characteristics of cancer stem cells 7 , 8 . However, the role of the CHST11 gene in ccRCC remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma

Hu,

Chen,

Zhang

et al. 2024

Sci Rep

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Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein–protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

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The aberrant cancer metabolic gene carbohydrate sulfotransferase 11 promotes non-small cell lung cancer cell metastasis via dysregulation of ceruloplasmin and intracellular iron balance

Cited by 10 publications

References 44 publications

Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma

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