MB-04: EXPRESSION OF CRMP1 INHIBITS CELL PROLIFERATION OF MEDULLOBLASTOMA AND IS REGULATED BY HMGA1

Many facets of the tumor biology of medulloblastoma (MB) have not been fully elucidated. Collapsin response mediator protein 1 (CRMP1) is a member of cytoplasmic family that regulates the development of central nervous system. Recent studies demonstrated that CRMP1 functioned as an invasion suppressor. We reported that high mobility group AT-hook 1 (HMGA1) contributed to tumor biology of MB and regulated cell growth and migration/invasion. Transcriptional profiling and quantitative RT-PCR revealed the increased expression of CRMP1 in HMGA1-depleted cells, suggesting that CRMP1 may be a downstream target of HMGA1 in MB. In this study, we showed HMGA1 is associated with the CRMP1 promoter by chromatin immunoprecipitation (ChIP) assay. Luciferase assay demonstrated a marked enhancement of CRMP1 transcription activity in HMGA1-depleted cells. Furthermore, quantitative RT-PCR revealed a significant negative correlation between HMGA1 and CRMP1 in 32 MB samples. To investigate the biological roles of CRMP1 in MB pathogenesis, we established MB clones stably expressing CRMP1. Functional analysis revealed that expression of CRMP1 significantly inhibited cell proliferation, migration, invasion, and formation of filopodia and stress fibers. Our data suggest that HMGA1 regulates CRMP1 expression and CRMP1 is involved in MB pathogenesis.