LLGL2 rescues nutrient stress by promoting leucine uptake in ER+ breast cancer
| العنوان: | LLGL2 rescues nutrient stress by promoting leucine uptake in ER+ breast cancer |
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| المؤلفون: | Lewyn Li, John M. Asara, Augustin Luna, Yasuhiro Saito, Senthil K. Muthuswamy, Chris Sander, Myles Brown, Brian Raught, Etienne Coyaud |
| المصدر: | Nature. 569:275-279 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Multidisciplinary, Cell growth, Cell, Cancer, Biology, medicine.disease, law.invention, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Breast cancer, Cell culture, law, 030220 oncology & carcinogenesis, medicine, Cancer research, Suppressor, Endocrine system, Receptor |
| الوصف: | Drosophila Lgl and its mammalian homologues, LLGL1 and LLGL2, are scaffolding proteins that regulate the establishment of apical-basal polarity in epithelial cells1,2. Whereas Lgl functions as a tumour suppressor in Drosophila1, the roles of mammalian LLGL1 and LLGL2 in cancer are unclear. The majority (about 75%) of breast cancers express oestrogen receptors (ERs)3, and patients with these tumours receive endocrine treatment4. However, the development of resistance to endocrine therapy and metastatic progression are leading causes of death for patients with ER+ disease4. Here we report that, unlike LLGL1, LLGL2 is overexpressed in ER+ breast cancer and promotes cell proliferation under nutrient stress. LLGL2 regulates cell surface levels of a leucine transporter, SLC7A5, by forming a trimeric complex with SLC7A5 and a regulator of membrane fusion, YKT6, to promote leucine uptake and cell proliferation. The oestrogen receptor targets LLGL2 expression. Resistance to endocrine treatment in breast cancer cells was associated with SLC7A5- and LLGL2-dependent adaption to nutrient stress. SLC7A5 was necessary and sufficient to confer resistance to tamoxifen treatment, identifying SLC7A5 as a potential therapeutic target for overcoming resistance to endocrine treatments in breast cancer. Thus, LLGL2 functions as a promoter of tumour growth and not as a tumour suppressor in ER+ breast cancer. Beyond breast cancer, adaptation to nutrient stress is critically important5, and our findings identify an unexpected role for LLGL2 in this process. |
| تدمد: | 1476-4687 0028-0836 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::b2328de4bb1e2382d00832e4a2a2cbd2Test https://doi.org/10.1038/s41586-019-1126-2Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........b2328de4bb1e2382d00832e4a2a2cbd2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764687 00280836 |
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