Aberrant SLC6A14 Expression Promotes Proliferation and Metastasis of Colorectal Cancer via Enhancing the JAK2/STAT3 Pathway

Mao, Hongli; Sheng, Jinxiu; Jia, Jinlin; Wang, Chang Yun; Zhang, Shanfeng; Li, Hongle; He, Fucheng

doi:10.2147/ott.s288709

Cited by 19 publications

(17 citation statements)

References 36 publications

(44 reference statements)

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“…The JAK2/STAT3 signaling pathway mediates the function of solute carrier family 6 member 14 (SLC6A14) to promote the proliferation and metastasis of colorectal cancer cells [ 34 ]. Interestingly, a previous study showed that when JAK2/STAT3 signaling pathway is activated, cancer cells tend to escape the immune surveillance and metastasize to distant organs through blood circulation, resulting in the formation of metastatic lesions [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Ribonucleotide reductase subunit M2 promotes proliferation and epithelial–mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma

et al. 2021

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Retinoblastoma (RB) is an intraocular malignant tumor that often occurs in children. Along with the improvement of treatment strategies, the cure rate of RB has increased significantly. However, the treatment of advanced and recurrent RB remains as a critical challenge. Therefore, studying the molecular mechanisms underlying the progression of RB is essential for the development of novel and effective therapeutic strategies. Through the analysis of a previously published microarray study, we found that ribonucleotide reductase subunit M2 (RRM2) was highly expressed in RB tissues as compared to normal tissues. The purpose of this study is to clarify the role and mechanism of RRM2 in regulating the progression of RB. We first demonstrated that RRM2 expression level in RB tissues and cell lines was significantly higher when compared to that in normal retinal tissue and cell lines, and high RRM2 expression level was associated with a poorer overall survival of patients. In RB cells, RRM2 overexpression promoted cell proliferation, migration, invasion and epithelial–mesenchymal transformation (EMT), while RRM2 silencing suppressed these biological features. Silencing RRM2 reduced the activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, and the presence of JAK2/STAT3 signaling pathway inhibitor INCB attenuated the effect of RRM2 overexpression. Collectively, our data indicate that RRM2 promotes the progression of RB by activating JAK2/STAT3 signaling pathway. Targeting RRM2/JAK2/STAT3 axis lays a theoretical foundation for the formulation of novel RB therapy.

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Section: Discussionmentioning

confidence: 99%

Ribonucleotide reductase subunit M2 promotes proliferation and epithelial–mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma

et al. 2021

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“…Indeed, Sikder et al first showed that SLC6A14 function favors cell proliferation and invasion in colon cancer LS174T cell line ( Sikder et al, 2020 ). In addition, Mao et al showed that SLC6A14 overexpression or knockdown, respectively, promotes or inhibits migration and proliferation of colorectal cancer cells (HCT-116 and Caco-2 cells) in vitro ( Mao et al, 2021 ). They also found that the pharmacological inhibitor α-MT inhibited cell proliferation and the fact that SLC6A14 promoted colorectal cancer cell proliferation and migration via the JAK2/STAT3 pathway.…”

Section: Discussionmentioning

confidence: 99%

SLC6A14 Impacts Cystic Fibrosis Lung Disease Severity via mTOR and Epithelial Repair Modulation

Mercier

Calmel

Mésinèle

et al. 2022

Front. Mol. Biosci.

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Cystic fibrosis (CF), due to pathogenic variants in CFTR gene, is associated with chronic infection/inflammation responsible for airway epithelium alteration and lung function decline. Modifier genes induce phenotype variability between people with CF (pwCF) carrying the same CFTR variants. Among these, the gene encoding for the amino acid transporter SLC6A14 has been associated with lung disease severity and age of primary airway infection by the bacteria Pseudomonas aeruginosa. In this study, we investigated whether the single nucleotide polymorphism (SNP) rs3788766, located within SLC6A14 promoter, is associated with lung disease severity in a large French cohort of pwCF. We also studied the consequences of this SNP on SLC6A14 promoter activity using a luciferase reporter and the role of SLC6A14 in the mechanistic target of rapamycin kinase (mTOR) signaling pathway and airway epithelial repair. We confirm that SLC6A14 rs3788766 SNP is associated with lung disease severity in pwCF (p = 0.020; n = 3,257, pancreatic insufficient, aged 6–40 years old), with the minor allele G being deleterious. In bronchial epithelial cell lines deficient for CFTR, SLC6A14 promoter activity is reduced in the presence of the rs3788766 G allele. SLC6A14 inhibition with a specific pharmacological blocker reduced 3H-arginine transport, mTOR phosphorylation, and bronchial epithelial repair rates in wound healing assays. To conclude, our study highlights that SLC6A14 genotype might affect lung disease severity of people with cystic fibrosis via mTOR and epithelial repair mechanism modulation in the lung.

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“…Indeed, Sikder et al rst showed that SLC6A14 function favors cell proliferation and invasion in colon cancer LS174T cell line (Sikder et al, 2020). In addition, Mao et al showed that SLC6A14 overexpression or knockdown respectively promotes or inhibits migration and proliferation of colorectal cancer cells (HCT-116 and Caco-2 cells) in vitro (Mao et al, 2021). They also found that the pharmacological inhibitor α-MT inhibited cell proliferation as well as the fact that SLC6A14 promoted colorectal cancer cell proliferation and migration via the JAK2/STAT3 pathway.…”

Section: Discussionmentioning

confidence: 99%

SLC6A14 impacts cystic fibrosis lung disease severity via mTOR and epithelial repair modulation

Mercier

Calmel

Mésinèle

et al. 2022

Preprint

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Cystic fibrosis (CF), due to variants in CFTR gene, is associated with chronic infection/inflammation responsible for airway epithelium alteration and lung function decline. Modifier genes induce phenotype variability between people with CF (pwCF) carrying the same CFTR variants. Among these, the gene encoding for the amino acid transporter SLC6A14 has been associated with lung disease severity and age of primary airway infection by the bacteria Pseudomonas aeruginosa. In this study, we investigated whether the single nucleotide polymorphism (SNP) rs3788766, located within SLC6A14 promoter, is associated with lung disease severity in a large French cohort of pwCF. We also studied the consequences of this SNP on SLC6A14 promoter activity using a luciferase reporter and the role of SLC6A14 in mammalian target of rapamycin (mTOR) signaling pathway and airway epithelial repair. We confirm that SLC6A14 rs3788766 SNP is associated with lung disease severity in pwCF (p=0.020; n=3,257, pancreatic insufficient, aged 6 to 40 years old), with the minor allele G being deleterious. In bronchial epithelial cell lines deficient for CFTR, SLC6A14 promoter activity is reduced in the presence of the rs3788766 G allele. SLC6A14 inhibition with a specific pharmacological blocker reduced 3H-arginine transport, mTOR phosphorylation and bronchial epithelial repair rates in wound healing assays. To conclude, our study highlights that SLC6A14 genotype might affect lung disease severity of people with cystic fibrosis via mTOR and epithelial repair mechanisms modulation in the lung.

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Aberrant SLC6A14 Expression Promotes Proliferation and Metastasis of Colorectal Cancer via Enhancing the JAK2/STAT3 Pathway

Cited by 19 publications

References 36 publications

Ribonucleotide reductase subunit M2 promotes proliferation and epithelial–mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma

Ribonucleotide reductase subunit M2 promotes proliferation and epithelial–mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma

SLC6A14 Impacts Cystic Fibrosis Lung Disease Severity via mTOR and Epithelial Repair Modulation

SLC6A14 impacts cystic fibrosis lung disease severity via mTOR and epithelial repair modulation

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