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.
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.
Authors: Kaustubh Wagh; Momoko Ishikawa; David A Garcia; Diana A Stavreva; Arpita Upadhyaya; Gordon L Hager Journal: Trends Cell Biol Date: 2021-03-09 Impact factor: 20.808
Authors: Simran Kaur; Mohammad Zeeshan Najm; Mohammad Aasif Khan; Naseem Akhter; Vyas M Shingatgeri; Mudra Sikenis; Abdulaziz A Aloliqi Journal: Breast Cancer (Dove Med Press) Date: 2021-12-14
Authors: Noa Furth; Ioannis S Pateras; Ron Rotkopf; Vassiliki Vlachou; Irina Rivkin; Ina Schmitt; Deborah Bakaev; Anat Gershoni; Elena Ainbinder; Dena Leshkowitz; Randy L Johnson; Vassilis G Gorgoulis; Moshe Oren; Yael Aylon Journal: Life Sci Alliance Date: 2018-10-30