title: Chromodomain Helicase/ATPase DNA-Binding Protein 1-Like Gene (CHD1L) Expression and Implications for Invasion and Metastasis of Breast Cancer.
abstract: BACKGROUND
  Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L), also known as ALC1 (amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.
  
  
  METHODS
  Immunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.
  
  
  RESULTS
  CHD1L overexpression was observed in 112 of 268 patients (41.8%). This overexpression was associated with lymph node metastasis (P = 0.008), tumor differentiation (P = 0.020), distant metastasis (P = 0.026), MMP-2 (P = 0.035), and MMP-9 expression (P = 0.022). In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.
  
  
  CONCLUSIONS
  CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.
authors.affiliation: Qing Dao University, Qingdao, PR China.|Clinical Department, Weifang Medical University, Weifang, PR China.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Mu
authors.affiliation: Medicine Research Center, Weifang Medical University, Weifang, 261053, PR China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Li
authors.affiliation: Affiliated Hospital of Qing Dao University, Qing dao, 260003, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Qing dao Central Hospital Qing Dao Tumor Hospital, the Second Affiliated hospital of Qing Dao University, Qing dao, 260042, PR China.
authors.forename: Shi-Chao
authors.initials: SC
authors.lastname: Liu
authors.affiliation: College of Nursing, Weifang Medical University, Weifang, 261053, PR China.
authors.forename: Chong-Gao
authors.initials: CG
authors.lastname: Yin
authors.affiliation: Qing dao Central Hospital Qing Dao Tumor Hospital, the Second Affiliated hospital of Qing Dao University, Qing dao, 260042, PR China.
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D034741:RNA, Small Interfering; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D004265:DNA Helicases; C546393:Chd1l protein, mouse