Llgl2 rescues nutrient stress by promoting leucine uptake in er+ breast cancer

Saito, Yasuhiro; Li, Lewyn; Coyaud, Etienne-Marie; Luna, Augustin; Sander, Chris; Raught, Brian; Asara, John M.; Brown, Myles; Muthuswamy, Senthil K.

Type de document :

Article dans une revue scientifique: Article original

DOI :

10.1038/s41586-019-1126-2

PMID :

30996345

URL permanente :

http://hdl.handle.net/20.500.12210/74983

Titre :

Llgl2 rescues nutrient stress by promoting leucine uptake in er+ breast cancer

Auteur(s) :

Saito, Yasuhiro [Auteur]
Li, Lewyn [Auteur]
Coyaud, Etienne-Marie [Auteur]
Luna, Augustin [Auteur]
Sander, Chris [Auteur]
Raught, Brian [Auteur]
Asara, John M. [Auteur]
Brown, Myles [Auteur]
Muthuswamy, Senthil K. [Auteur]

Titre de la revue :

Nature

Nom court de la revue :

Nature

Numéro :

569

Pagination :

Date de publication :

2019-05-09

ISSN :

0028-0836

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Drosophila Lgl and its mammalian homologues, LLGL1 and LLGL2, are scaffolding proteins that regulate the establishment of apical-basal polarity in epithelial cells(1,2). Whereas Lgl functions as a tumour suppressor in ...
Lire la suite >Drosophila Lgl and its mammalian homologues, LLGL1 and LLGL2, are scaffolding proteins that regulate the establishment of apical-basal polarity in epithelial cells(1,2). Whereas Lgl functions as a tumour suppressor in Drosophila(1), 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 treatment(4). However, the development of resistance to endocrine therapy and metastatic progression are leading causes of death for patients with ER(+) disease(4). 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 important(5), and our findings identify an unexpected role for LLGL2 in this process.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

INSERM
Université de Lille

Collections :

Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Date de dépôt :

2022-06-15T13:57:41Z

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