Role of Amino Acid Transporter Expression as a Prognostic Marker in Patients With Surgically Resected Colorectal Cancer

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

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Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

British Journal of Cancer ◽

10.1038/bjc.2014.178 ◽

2014 ◽

Vol 110 (10) ◽

pp. 2506-2513 ◽

Cited By ~ 68

Author(s):

M Toyoda ◽

K Kaira ◽

Y Ohshima ◽

N S Ishioka ◽

M Shino ◽

...

Keyword(s):

Amino Acid ◽

Tongue Cancer ◽

Prognostic Significance ◽

Amino Acid Transporter ◽

Acid Transporter ◽

Transporter Expression

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L-Type Amino Acid Transporter 1 Immunoreactivity as a Possible Diagnostic and Prognostic Marker of Thymic Carcinoma

The Tohoku Journal of Experimental Medicine ◽

10.1620/tjem.246.167 ◽

2018 ◽

Vol 246 (3) ◽

pp. 167-174 ◽

Cited By ~ 2

Author(s):

Sumiko Maeda ◽

Yoshimasa Nakazato ◽

Keitaro Hayashi ◽

Morimichi Nishihira ◽

Takashi Inoue ◽

...

Keyword(s):

Amino Acid ◽

Prognostic Marker ◽

Thymic Carcinoma ◽

Amino Acid Transporter ◽

Acid Transporter

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Circular RNA NF1-419 Inhibits Proliferation and Induces Apoptosis by Regulating Lipid Metabolism in Astroglioma Cells

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210729125802 ◽

2021 ◽

Vol 16 ◽

Author(s):

Ran Li ◽

Xiaocui Tang ◽

Changqiong Xu ◽

Yinrui Guo ◽

Longkai Qi ◽

...

Keyword(s):

Lipid Metabolism ◽

Amino Acid ◽

Tumor Growth ◽

Ganoderma Lucidum ◽

Amino Acid Transporter ◽

Cationic Amino Acid Transporter ◽

Cationic Amino Acid ◽

Acid Transporter ◽

Astroglioma Cells

Background: Astroglioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for astroglioma. In the present study, the extract (L3) from Ganoderma Lucidum (G.lucidum) was found to inhibit the growth of astroglioma U87 cells and change the expression of circular RNAs (circRNAs). One of these, including the circular NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene. Objective: The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown. This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma cells and aims to elaborate on its regulatory mechanism. Methods: The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor growth and metabolic regulation. Finally, we used docking screening to identify compounds in G. lucidum extracts that target circ-419. Results: U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels (L-VOCC), phospholipase C-β3 (PLCβ3), Mucin1, cationic amino acid transporter 4 (CAT4), cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited, while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3 could activate circNF1-419 in astroglioma treatment. Conclusion: This study indicated that circNF1-419 could be a therapeutic target for the clinical treatment of astroglioma. L3 from Ganoderma Lucidum (G.lucidum) could inhibit astroglioma growth by activating circNF1-419.

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Anti‐tumor effects of an antagonistic mAb against the ASCT2 amino acid transporter on KRAS ‐mutated human colorectal cancer cells

Cancer Medicine ◽

10.1002/cam4.2689 ◽

2019 ◽

Vol 9 (1) ◽

pp. 302-312 ◽

Cited By ~ 6

Author(s):

Yuta Hara ◽

Yushi Minami ◽

Soshi Yoshimoto ◽

Natsumi Hayashi ◽

Akitaka Yamasaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Amino Acid ◽

Cancer Cells ◽

Amino Acid Transporter ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Acid Transporter ◽

Human Colorectal Cancer Cells

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Downregulation of Placental Amino Acid Transporter Expression and mTORC1 Signaling Activity Contributes to Fetal Growth Retardation in Diabetic Rats

International Journal of Molecular Sciences ◽

10.3390/ijms21051849 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1849

Author(s):

Jie Xu ◽

Jiao Wang ◽

Yang Cao ◽

Xiaotong Jia ◽

Yujia Huang ◽

...

Keyword(s):

Amino Acid ◽

Rat Model ◽

Amino Acid Transporter ◽

Amino Acid Transporters ◽

Amino Acid Transport System ◽

Intrauterine Growth ◽

System L ◽

Acid Transporter ◽

Transporter Expression

Alterations in placental transport may contribute to abnormal fetal intrauterine growth in pregnancies complicated by diabetes, but it is not clear whether the placental amino acid transport system is altered in diabetic pregnancies. We therefore studied the changes in the expressions of placental amino acid transporters in a rat model of diabetes induced by streptozotocin, and tested the effects of hyperglycemia on trophoblast amino acid transporter in vitro. Our results showed that the expressions for key isoforms of system L amino acid transporters were significantly reduced in the placentas of streptozotocin-induced diabetic pregnant rats, which was associated with the decreased birthweight in the rats. A decreased placental efficiency and decreased placental mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity were also found in the rat model. In addition, hyperglycemia in vitro could inhibit amino acid transporter expression and mTORC1 activity in human trophoblast. Inhibition of mTORC1 activity led to reduced amino acid transporter expression in placental trophoblast. We concluded that reduced placental mTORC1 activity during pregnancy resulted in decreased placental amino acid transporter expression and, subsequently, contributed to fetal intrauterine growth restriction in pregnancies complicated with diabetes.

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