Targeting L-type amino acid transporter 1 in urological malignancy: Current status and future perspective

Pae, Sangjon; Sakamoto, Shinichi; Zhao, Xue; Saito, Shingo; Tamura, Tomohiro; Imamura, Yusuke; Sazuka, Tomokazu; Reien, Yoshie; Hirayama, Yuri; Hashimoto, Hirofumi; Kanai, Yoshikatsu; Ichikawa, Tomohiko; Anzai, Naohiko

doi:10.1016/j.jphs.2022.10.002

Cited by 4 publications

(3 citation statements)

References 62 publications

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“…High cellular leucine concentration activates the mTOR pathway and promotes cell proliferation [ 20 ]. SLC7A5 is known to be highly expressed in many cancers [ 21 , 22 ]. In KRAS-mutant colorectal cancer cells, SLC7A5 maintained intracellular amino acid level and activated mTOR pathway, which finally supported cell proliferation [ 23 ]; in small cell lung cancer, increased SLC7A5 promoted cell growth [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay

Wu,

Fang,

et al. 2024

Mol Biomed

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Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan–Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

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Section: Introductionmentioning

confidence: 99%

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay

Wu,

Fang,

et al. 2024

Mol Biomed

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“…11,12 The LAT1 protein encoded by the SLC7A5 gene forms a disulfide bond with glycoprotein 4F2hc. 13 Functioning as an antiporter system, LAT1 and 4F2hc facilitate the cellular uptake of neutral BCAAs such as Leu, and the efflux of Gln, which is a critical pathway for EAA entry into the cell. 14,15 LAT1-4F2hc regulates intracellular AA flux, playing an essential role in mTOR regulation.…”

Section: Introductionmentioning

confidence: 99%

“…It is suggested that optimal AA regulation S6K1 and 4EBP1 phosphorylation by promoting mTOR phosphorylation, and thus promoting casein synthesis. , The availability of AA in the mammary gland is important not only for protein synthesis but also for the rate of AA transport. LAT1, first isolated by Kanai in 1998, encodes a novel Na + -independent multipass transmembrane protein for neutral amino acids localized to the cell membrane. , The LAT1 protein encoded by the SLC7A5 gene forms a disulfide bond with glycoprotein 4F2hc . Functioning as an antiporter system, LAT1 and 4F2hc facilitate the cellular uptake of neutral BCAAs such as Leu, and the efflux of Gln, which is a critical pathway for EAA entry into the cell. , LAT1-4F2hc regulates intracellular AA flux, playing an essential role in mTOR regulation .…”

Section: Introductionmentioning

confidence: 99%

Leucine-Mediated SLC7A5 Promotes Milk Protein and Milk Fat Synthesis through mTOR Signaling Pathway in Goat Mammary Epithelial Cells

Ni,

Yue,

Tian

et al. 2024

J. Agric. Food Chem.

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The SLC7A5 gene encodes a Na + and pH-independent transporter protein that regulates cell growth by regulating the uptake of AA. This study, utilizing RNA-seq, aimed to explore the effect of SLC7A5 on the synthesis of milk proteins and fats in goat mammary epithelial cells (GMECs) through gene interference and overexpression techniques. The results demonstrated that the overexpression of SLC7A5 resulted in a significant increase in the expression of CSN1S1, SCD, CEBPB, ACACA, α S1 -casein, p-S6K, and p-S6. The levels of p-S6K and p-S6 gradually increased as the AA/Leu stimulation time lengthened. The overexpression of SLC7A5 rescued the role of Torin1 in GMECs. In conclusion, SLC7A5 plays a crucial role in promoting the synthesis of milk proteins and milk fats through the mTOR signaling pathway in GMECs, providing a theoretical foundation for improving the quality of goat milk.

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Enhancing fengycin production in the co-culture of Bacillus subtilis and Corynebacterium glutamicum by engineering proline transporter

Gao

Wei

Ding

et al. 2023

Bioresource Technology

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Targeting L-type amino acid transporter 1 in urological malignancy: Current status and future perspective

Cited by 4 publications

References 62 publications

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay

Leucine-Mediated SLC7A5 Promotes Milk Protein and Milk Fat Synthesis through mTOR Signaling Pathway in Goat Mammary Epithelial Cells

Enhancing fengycin production in the co-culture of Bacillus subtilis and Corynebacterium glutamicum by engineering proline transporter

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