title: Chk1 as a new therapeutic target in triple-negative breast cancer.
abstract: OBJECTIVE
  Bioinformatics analyses of pathways and genes differentially expressed between malignant and benign lesions could allow discovering new therapeutic targets. Here, we identified Checkpoint kinase 1 (Chk1) as a potent therapeutic target in triple-negative breast cancer (TNBC).
  
  
  METHODS
  Differential gene expression between TNBC, other malignant and benign lesions was performed on two breast cancer datasets. Chk1 was targeted using RNA interference or chemical inhibitor in several TNBC cell lines.
  
  
  RESULTS
  DNA repair pathway was identified as one mostly deregulated pathway in TNBC as compared to benign lesions. Chk1 was identified as candidate target among the 35 genes included in this pathway. Gene expression analysis revealed that Chk1 gene was significantly overexpressed in TNBC as compared to non-TNBC and benign lesions. Depletion of Chk1 protein expression induced a marked reduction of cell viability and led to mitotic catastrophe in TNBC cells. Chemical Chk1 inhibitor decreased survival in TNBC cells, and transcriptome analyze revealed a modulation of gene expression profile in response to Chk1 treatment.
  
  
  CONCLUSIONS
  These findings suggest that Chk1 may represent a therapeutic target in TNBC, and provide a rationale to evaluate Chk1 inhibitors in breast cancer patients.
authors.affiliation: Department of Medical Oncology, Villejuif F-94800, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Goubar
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Scott
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vicier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lefèbvre
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Samar
authors.initials: S
authors.lastname: Alsafadi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Commo
authors.affiliation: Department of Medical Oncology, Villejuif F-94800, France.
authors.forename: Mahasti
authors.initials: M
authors.lastname: Saghatchian
authors.affiliation: Plateforme de Biologie Intégrée, Institut de cancérologie Gustave Roussy, Villejuif F-94800, France.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.affiliation: Plateforme de Biologie Intégrée, Institut de cancérologie Gustave Roussy, Villejuif F-94800, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.affiliation: Department of Medical Oncology, Villejuif F-94800, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: Department of Medical Oncology, Villejuif F-94800, France; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France. Electronic address: fabrice.andre@gustaveroussy.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR981, Villejuif F-94800, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Quidville
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D004260:DNA Repair / Q000187:drug effects; D058492:Drug Repositioning; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics*; D034622:RNA Interference; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000628:therapy
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: Cell growth; Chk1; Mitotic catastrophe; Triple-negative breast cancer