Inhibition of the amino‐acid transporter LAT1 demonstrates anti‐neoplastic activity in medulloblastoma
| العنوان: | Inhibition of the amino‐acid transporter LAT1 demonstrates anti‐neoplastic activity in medulloblastoma |
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| المؤلفون: | Yann Cormerais, Sandra Schrötter, Hitoshi Endou, Vincent Picco, Gilles Pages, Michael F. Wempe, Sandy Giuliano, Jacques Pouysségur, Eric Tambutté, Marina Pagnuzzi-Boncompagni |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | John Wiley and Sons Inc., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Primary Cell Culture, Antineoplastic Agents, mTORC1, Mechanistic Target of Rapamycin Complex 1, Protein Serine-Threonine Kinases, medulloblastoma, Cell Line, Large Neutral Amino Acid-Transporter 1, 03 medical and health sciences, Therapeutic approach, Mice, 0302 clinical medicine, Cell Line, Tumor, Cerebellum, Medicine, Animals, Humans, Amino acid transporter, ATF4, Cerebellar Neoplasms, Child, Cell Proliferation, Medulloblastoma, Neurons, Benzoxazoles, amino acid transport, business.industry, Cell Biology, Original Articles, medicine.disease, Embryo, Mammalian, Activating Transcription Factor 4, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Cell culture, Organ Specificity, 030220 oncology & carcinogenesis, Astrocytes, Cancer cell, Cancer research, Molecular Medicine, Tyrosine, Original Article, GCN2, business, Homeostasis |
| الوصف: | Most cases of medulloblastoma (MB) occur in young children. While the overall survival rate can be relatively high, current treatments combining surgery, chemo‐ and radiotherapy are very destructive for patient development and quality of life. Moreover, aggressive forms and recurrences of MB cannot be controlled by classical therapies. Therefore, new therapeutic approaches yielding good efficacy and low toxicity for healthy tissues are required to improve patient outcome. Cancer cells sustain their proliferation by optimizing their nutrient uptake capacities. The L‐type amino acid transporter 1 (LAT1) is an essential amino acid carrier overexpressed in aggressive human cancers that was described as a potential therapeutic target. In this study, we investigated the therapeutic potential of JPH203, a LAT1‐specific pharmacological inhibitor, on two independent MB cell lines belonging to subgroups 3 (HD‐MB03) and Shh (DAOY). We show that while displaying low toxicity towards normal cerebral cells, JPH203 disrupts AA homeostasis, mTORC1 activity, proliferation and survival in MB cells. Moreover, we demonstrate that a long‐term treatment with JPH203 does not lead to resistance in MB cells. Therefore, this study suggests that targeting LAT1 with JPH203 is a promising therapeutic approach for MB treatment. |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6b7d5b0eb4ae5a104afabdebffbfc59Test http://europepmc.org/articles/PMC6433660Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d6b7d5b0eb4ae5a104afabdebffbfc59 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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