LATS2 is a modulator of estrogen receptor alpha

BACKGROUND Estrogen Receptor a (ERa), 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 ERa-positive; however, a proportion becomes resistant. Phosphorylation of ERa 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 ERa. MATERIALS AND METHODS The role of LATS2 on activation of ERa transcription and its functional consequences was examined by various molecular and cellular biology techniques. RESULTS LATS2 co-localises with ERa in the nucleus. LATS2-silencing increases expression of ERa-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 ERa activity is relevant to therapeutics. LATS2 modulates ERa-regulated gene transcription, through direct and/or indirect interactions with ERa.