title: E1A-mediated inhibition of HSPA5 suppresses cell migration and invasion in triple-negative breast cancer.
abstract: BACKGROUND
  Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients.
  
  
  METHODS
  The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models.
  
  
  RESULTS
  The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model.
  
  
  CONCLUSIONS
  The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chen
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Tseng
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Chiu
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Hong
authors.forename: Weu
authors.initials: W
authors.lastname: Wang
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Jui-Ti
authors.initials: JT
authors.lastname: Ma
authors.forename: Chung-Hsing
authors.initials: CH
authors.lastname: Chen
authors.forename: Shih-Sheng
authors.initials: SS
authors.lastname: Jiang
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.forename: Ming-Te
authors.initials: MT
authors.lastname: Huang
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D017500:Adenovirus E1A Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse