title: CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration.
abstract: Coiled-coil-helix-coiled-coil-helix domain-containing 2, a mitochondrial protein, encoded by CHCHD2 is located at chromosome 7p11.2 and proximal to the EGFR gene. Here, bioinformatic analyses revealed that CHCHD2 is consistently coamplified with EGFR in non-small cell lung carcinoma (NSCLC). In addition, CHCHD2 and EGFR protein expression levels were positively correlated and upregulated relative to normal lung in NSCLC tumor-derived xenografts. Knockdown of CHCHD2 expression in NSCLC cells attenuated cell proliferation, migration, and mitochondrial respiration. CHCHD2 protein-protein interactions were assessed by the complementary approaches of affinity purification mass spectrometry and in vivo proximity ligation. The CHCHD2 interactome includes the apparent hub proteins C1QBP (a mitochondrial protein) and YBX1 (an oncogenic transcription factor), and an overlapping set of hub-associated proteins implicated in cell regulation.
  
  
  CONCLUSIONS
  CHCHD2 influences mitochondrial and nuclear functions and contributes to the cancer phenotype associated with 7p11.2 amplification in NSCLC.
authors.affiliation: Program in Molecular Structure and Function, Hospital For Sick Children, Toronto, Ontario, Canada.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Ravi N
authors.initials: RN
authors.lastname: Vellanki
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Coyaud
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ignatchenko
authors.affiliation: Program in Molecular Structure and Function, Hospital For Sick Children, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Program in Molecular Structure and Function, Hospital For Sick Children, Toronto, Ontario, Canada.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Krieger
authors.affiliation: Program in Molecular Structure and Function, Hospital For Sick Children, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.affiliation: Program in Molecular Structure and Function, Hospital For Sick Children, Toronto, Ontario, Canada.
authors.forename: Jiefei
authors.initials: J
authors.lastname: Tong
authors.affiliation: Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Nhu-An
authors.initials: NA
authors.lastname: Pham
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Medical Oncology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bradly G
authors.initials: BG
authors.lastname: Wouters
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.affiliation: Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ming Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Program in Molecular Structure and Function, Hospital For Sick Children, Toronto, Ontario, Canada. Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. m.moran@utoronto.ca.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Moran
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002846:Chromatography, Affinity; D002897:Chromosomes, Human, Pair 7; D019295:Computational Biology; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism
chemical_list: C087299:C1QBP protein, human; C580880:CHCHD2 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D020543:Proteome; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors