title: Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells.
abstract: BACKGROUND
  The SWI/SNF ATP dependent chromatin remodeling complex is a multi-subunit complex, conserved in eukaryotic evolution that facilitates nucleosomal re-positioning relative to the DNA sequence. In recent years the SWI/SNF complex has emerged to play a role in cancer development as various sub-units of the complex are found to be mutated in a variety of tumors. One core-subunit of the complex, which has been well established as a tumor suppressor gene is SMARCB1 (SNF5/INI1/BAF47). Mutation and inactivation of SMARCB1 have been identified as the underlying mechanism leading to Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms.
  
  
  METHODS
  We present a phosphoproteomic study of Smarcb1 dependent changes in signaling networks. The SILAC (Stable Isotopic Labeling of Amino Acids in Cell Culture) protocol was used to quantify in an unbiased manner any changes in the phosphoproteomic profile of Smarcb1 deficient murine rhabdoid tumor cell lines following Smarcb1 stable re-expression and under different serum conditions.
  
  
  RESULTS
  This study illustrates broad changes in the regulation of multiple biological networks including cell cycle progression, chromatin remodeling, cytoskeletal regulation and focal adhesion. Specifically, we identify Smarcb1 dependent changes in phosphorylation and expression of the EGF receptor, demonstrate downstream signaling and show that inhibition of EGFR signaling specifically hinders the proliferation of Smarcb1 deficient cells.
  
  
  CONCLUSIONS
  These results support recent findings regarding the effectivity of EGFR inhibitors in hindering the proliferation of human MRT cells and demonstrate that activation of EGFR signaling in Rhabdoid tumors is SMARCB1 dependent.
authors.affiliation: Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. Jonatan.darr@mail.huji.ac.il.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Darr
authors.affiliation: Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. agnesk@mail.huji.ac.il.
authors.forename: Agnes
authors.initials: A
authors.lastname: Klochendler
authors.affiliation: Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. sarai@ekmd.huji.ac.il.
authors.forename: Sara
authors.initials: S
authors.lastname: Isaac
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Geiger@tauex.tau.ac.il.
authors.forename: Tamar
authors.initials: T
authors.lastname: Geiger
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Geiger@tauex.tau.ac.il.
authors.forename: Tami
authors.initials: T
authors.lastname: Geiger
authors.affiliation: Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. eden@vms.huji.ac.il.
authors.forename: Amir
authors.initials: A
authors.lastname: Eden
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007553:Isotope Labeling; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D040901:Proteomics; D018335:Rhabdoid Tumor / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D015398:Signal Transduction
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D010750:Phosphoproteins; D000071796:SMARCB1 Protein; C513265:Smarcb1 protein, mouse; C541485:EGFR protein, mouse; D066246:ErbB Receptors