We established cellular models in MDA-MB-231 and immortalized primary epithelial cells to study the effect of KHDRBS3 and SRSF12 on tumor progression and metastasis (Task1). We analyzed the effect of KHDRBS3 depletion on the growth and migration properties of the MDABD-231 cells in vitro (Task 1) and their ability to form tumors and metastasize in mouse xenograft models (Task 2). The results of similar experiments for SRPK1 were recently published and demonstrated a role for SRPK1 in migration and tumor formation. Instead of repeating the published work we expanded Task 3 to include a KHDRBS3 knockout mouse model in addition to the SRPK1 knockout mouse in the experiments aimed to determine their role for tumor initiation, progression and metastasis in vivo. The mouse strains are at hand and we will start analyzing the effects of the knockouts on tumor growth during the second year of this project. Continued analysis of the splicing factor expression in primary tumor samples further supports strong association of KHDRBS3 with triple negative breast carcinoma (Task4). Finally, RNASeq was used to determine the effect of KHDRBS3 and SRPK1 depletion on the transcriptome of MDA-MB-231 cells (Task 6).