Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer

This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients

Online Classroom dengan Pemanfaatan K12lessonplans Bagi Guru-guru SMP. H. Isriati Semarang

This society service is carried out using a free teacher website;www.k12lessonplans.com, in a form of training for teachers at SMP. H.Isriati Semarang. There are 15 teachers joining this training, which is heldon 14 ?óÔé¼ÔÇ£ 16 July, 2012, starting from 09:00 am - 02:00 pm. This trainingtakes place in the Computer Laboratory group and individual audience isconducted consecutively from 17 ?óÔé¼ÔÇ£ 21 July, 2012 and 23 ?óÔé¼ÔÇ£ 26 July startingfrom 02:00 ?óÔé¼ÔÇ£ 04:00 pm in the teachers?óÔé¼Ôäó longue at the school. This programis aimed to give the teachers knowledge and training, to implement onlineclassroom using the website. The methods used in this program are;explanation, question and answer, training and group guidance

Additional file 5: of Phosphorylation-dependent regulation of ALDH1A1 by Aurora kinase A: insights on their synergistic relationship in pancreatic cancer

Raw data for Fig. 6d, e, h, and k. (XLSX 42 kb