Related Experiment Video
Updated: May 15, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
LATS2 is a modulator of estrogen receptor alpha
Lei Cheng Lit1, Susan Scott, Hua Zhang
1Department of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Background:
Estrogen Receptor α (ERα), a member of the nuclear receptor superfamily of transcription factors, plays a central role in breast cancer development. More than two-thirds of patients with breast cancer are ERα-positive; however, a proportion becomes resistant. Phosphorylation of ERα is one of the mechanisms associated with resistance to endocrine therapy. In a kinome screen, we have identified the large tumor suppressor homolog-2 (LATS2) as a potential kinase, acting on ERα.
Materials And Methods:
The role of LATS2 on activation of ERα transcription and its functional consequences was examined by various molecular and cellular biology techniques.
Results:
LATS2 co-localises with ERα in the nucleus. LATS2-silencing increases expression of ERα-regulated genes and inhibits proliferation. At the protein level, inhibition of LATS2 reduces the expression of cyclin-D1 and Nuclear Receptor Co-Repressor (NCoR) while increasing the expression of p27.
Conclusion:
Identifying novel kinases which modulate ERα activity is relevant to therapeutics. LATS2 modulates ERα-regulated gene transcription, through direct and/or indirect interactions with ERα.
Insights
Large tumor suppressor homolog-2 (LATS2) kinase modulates Estrogen Receptor α (ERα) activity, impacting ERα-regulated gene transcription and breast cancer cell proliferation. This finding is relevant for developing new endocrine therapies.
Area of Science:
- Molecular Biology
- Cancer Research
- Endocrinology
Background:
- Estrogen Receptor α (ERα) is crucial in breast cancer, with resistance to endocrine therapy a significant clinical challenge.
- ERα phosphorylation is implicated in endocrine resistance mechanisms.
- Large tumor suppressor homolog-2 (LATS2) was identified as a potential kinase targeting ERα.
Purpose of the Study:
- To investigate the role of LATS2 in ERα transcriptional activation.
- To determine the functional consequences of LATS2 modulation on ERα activity and breast cancer cell behavior.
Main Methods:
- Utilized molecular and cellular biology techniques.
- Examined LATS2's effect on ERα-regulated gene expression and cell proliferation.
- Analyzed protein level changes including cyclin-D1, NCoR, and p27.
Main Results:
- LATS2 co-localizes with ERα in the nucleus.
- LATS2 silencing enhanced ERα-regulated gene expression and inhibited cell proliferation.
- LATS2 inhibition decreased cyclin-D1 and NCoR, while increasing p27 expression.
Conclusions:
- LATS2 modulates ERα-regulated gene transcription via direct and/or indirect interactions.
- Understanding LATS2's role in ERα signaling offers potential therapeutic avenues for breast cancer.
Related Concept Videos
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of Nuclear Protein Sorting
lncRNA - Long Non-coding RNAs
Intracellular Hormone Receptors
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with one...
Operons
