Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer

• Published in: Nature medicine Vol. 17; no. 6; pp. 715 - 719
• Main Authors: Giamas, Georgios, Filipović, Aleksandra, Jacob, Jimmy, Messier, Walter, Zhang, Hua, Yang, Dongyun, Zhang, Wu, Shifa, Belul Assefa, Photiou, Andrew, Tralau-Stewart, Cathy, Castellano, Leandro, Green, Andrew R, Coombes, R Charles, Ellis, Ian O, Ali, Simak, Lenz, Heinz-Josef, Stebbing, Justin
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2011; Nature Publishing Group
• Subjects: 631/67/1059/602; 631/80/86; 692/699/67/1347; Animals; Antineoplastic Agents, Hormonal - therapeutic use; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - physiopathology; Cancer Research; Care and treatment; Drug Resistance, Neoplasm - genetics; Estrogen; Estrogen Receptor alpha - biosynthesis; Estrogen Receptor alpha - metabolism; Estrogen Receptor alpha - physiology; Female; Gene Expression Regulation, Neoplastic - physiology; Genes; Genetic aspects; Genotype; Humans; Infectious Diseases; letter; Metabolic Diseases; Mice; Mice, Nude; Molecular Medicine; Neoplasm Transplantation; Neurosciences; Physiological aspects; Polymorphism, Genetic - genetics; Protein kinases; Receptors; RNA, Small Interfering - physiology; Tamoxifen - therapeutic use; United States; United Kingdom

This report identifies LMTK3 kinase as a regulator of ERα activity. LMTK3 exerts its effects through direct interaction and indirectly through regulation of PKC, AKT and FOXO3's effects on ERα transcription and stability. LMTK3 can modulate tamoxifen responses and is a poor prognostic factor in...