title: CRMP1 Inhibits Proliferation of Medulloblastoma and Is Regulated by HMGA1.
abstract: 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 of proteins that regulate the development of central nervous system. Recent studies demonstrated that CRMP1 could function as an invasion suppressor. We reported previously that high mobility group AT-hook 1 (HMGA1) contributed to development of MB and regulated its growth and migration/invasion. Transcriptional profiling and quantitative RT-PCR revealed 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 can bind 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 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 proliferation, migration, invasion and formation of filopodia and intense stress fiber of MB cells. Our data suggest that HMGA1 regulates CRMP1 expression and CRMP1 is implicated in MB pathogenesis.
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, No.10, 2nd Yuexing Road, Nanshan District, Shenzhen, China.
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, China.
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China.
authors.forename: Kin-Mang
authors.initials: KM
authors.lastname: Lau
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, No.10, 2nd Yuexing Road, Nanshan District, Shenzhen, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D055815:Young Adult; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D025741:HMGA1a Protein; D009419:Nerve Tissue Proteins; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1