title: Inhibition of SHP2 in basal-like and triple-negative breast cells induces basal-to-luminal transition, hormone dependency, and sensitivity to anti-hormone treatment.
abstract: BACKGROUND
  The Src homology phosphotyrosyl phosphatase 2 (SHP2) is a positive effector of cell growth and survival signaling as well transformation induced by multiple tyrosine kinase oncogenes. Since the basal-like and triple-negative breast cancer (BTBC) is characterized by dysregulation of multiple tyrosine kinase oncogenes, we wanted to determine the importance of SHP2 in BTBC cell lines.
  
  
  METHODS
  Short hairpin RNA-based and dominant-negative expression-based SHP2 inhibition techniques were used to interrogate the functional importance of SHP2 in BTBC cell biology. In addition, cell viability and proliferation assays were used to determine hormone dependency for growth and sensitivity to anti-estrogen treatment.
  
  
  RESULTS
  We show that inhibition of SHP2 in BTBC cells induces luminal-like epithelial morphology while suppressing the mesenchymal and invasive property. We have termed this process as basal-to-luminal transition (BLT). The occurrence of BLT was confirmed by the loss of the basal marker alpha smooth muscle actin and the acquisition of the luminal marker cytokeratin 18 (CK18) expression. Furthermore, the occurrence of BLT led to estrogen receptor alpha (ERα) expression, hormone dependency, and sensitivity to tamoxifen treatment.
  
  
  CONCLUSIONS
  Our data show that inhibition of SHP2 induces BLT, ERα expression, dependency on estrogen for growth, and sensitivity to anti-hormone therapy. Therefore, inhibition of SHP2 may provide a therapeutic benefit in basal-like and triple-negative breast cancer.
authors.affiliation: Department of Biochemistry and The Marry Babb Randolph Cancer Center School of Medicine, West Virginia University, Morgantown, WV, 26506, USA. ttangela168@gmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and The Marry Babb Randolph Cancer Center School of Medicine, West Virginia University, Morgantown, WV, 26506, USA. yagazie@hsc.wvu.edu.
authors.forename: Yehenew M
authors.initials: YM
authors.lastname: Agazie
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D004967:Estrogens / Q000378:metabolism; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000473:pathology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D034741:RNA, Small Interfering; D013629:Tamoxifen; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11