379 Downregulating KIF4A significantly suppressed growth of uterine leiomyosarcoma

Introduction/Background* Uterine leiomyosarcoma (LMS) is notorious for its poor prognosis. New therapeutics strategy for LMS is mandatory. Kinesin family member4A (KIF4A) is a member of the kinesin4 subfamily and plays an important role in cell division. In recent years, KIF4A is revealed to plays significant roles in some cancers with tumor proliferation. The aim of this study is to investigate the role of KIF4A in LMS. Methodology To identify novel biomarkers of LMS, we performed shotgun proteomics of one normal human uterine smooth muscle cell line (UtSMC) and three LMS cell lines, SK-LMS, SKN and SK-UT1, using isobaric tags for relative and absolute quantitation (iTRAQ). Cell variability was evaluated by MST-8 assay in original LMS cells and KIF4A suppressed cells with siRNA in vitro. For evaluation of proliferation in vivo, we established KIF4A knockdown cell lines using shRNA and injected them subcutaneously to 6weeks ICR nude mice and evaluated changes in tumor size over time. To elucidate the mechanism, we performed cell cycle analysis by fluorescence-activated cell sorting (FACS) and western blotting. Result(s)* A total of 2084 proteins were identified using iTRAQ. KIF4A was identified as a protein with more than twice the expression level of normal smooth muscle cells. By western blotting, all three LMS cell line had expressed KIF4A. KIF4A downregulation significantly suppressed the growth of those cell lines in vitro (-37.2±4.73% in SK-LMS, -87.7±4.02% in SKN and -28.1±3.00% in SK-UT1, p Conclusion* We identified a novel expressed protein, KIF4A, which can be a therapeutic target for uterine leiomyosarcoma.