Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:LLGL2 rescues nutrient stress by promoting leucine uptake in ER
+
breast cancer. 3099 45
