title: Proteomic profiling of isogenic primary and metastatic medulloblastoma cell lines reveals differential expression of key metastatic factors.
abstract: Medulloblastoma is the most common malignant brain tumor in children. Around 30% of medulloblastoma patients are diagnosed with metastasis, which often results in a poor prognosis. Unfortunately, molecular mechanisms of medulloblastoma metastasis remain largely unknown. In this study, we employed the recently developed deep proteome analysis approach to quantitatively profile the expression of >10,000 proteins from CHLA-01-MED and CHLA-01R-MED isogenic cell lines derived from the primary and metastatic tumor of the same patient diagnosed with a group IV medulloblastoma. Using statistical analysis, we identified ~1400 significantly altered proteins between the primary and metastatic cell lines including known factors such as placental growth factor (PLGF), LIM homeobox 1 (LHX1) and prominim 1 (PROM1), as well as the negative regulator secreted protein acidic and cysteine rich (SPARC). Additional transwell experiments and immunohistochemical analysis of clinical medulloblastoma samples implicated yes-associated protein 1 (YAP1) as a potential key factor contributing to metastasis. Taken together, our data broadly defines the metastasis-relevant regulated proteome and provides a precious resource for further investigating potential mechanisms of medulloblastoma metastasis.
  
  
  
  This study represented the first deep proteome analysis of metastatic medulloblastomas and provided a valuable candidate list of altered proteins in metastatic medulloblastomas. The primary data suggested YAP1 as a potential driver for the metastasis of medulloblastoma. These results open up numerous avenues for further investigating the underlying mechanisms of medulloblastoma metastasis and improving the prognosis of medulloblastoma patients.
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pathology Center, School of Medicine, Shanghai Children's Medical, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Minzhi
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China. Electronic address: zhixiangwu@yahoo.com.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China. Electronic address: wuymsh@163.com.
authors.forename: Yeming
authors.initials: Y
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008527:Medulloblastoma / Q000473:pathology* / Q000556:secondary; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: Deep proteome; Isogenic cell lines; Medulloblastoma; Metastasis; Quantitative proteomics; YAP1