title: Tipping the balance between good and evil: aberrant 14-3-3ζ expression drives oncogenic TGF-β signaling in metastatic breast cancers.
abstract: Transforming growth factor beta (TGF-β) readily suppresses the development of early-stage breast cancers, an activity that gives way to tumor promotion in their late-stage counterparts. The molecular mechanisms underlying this mysterious switch in TGF-β function remain murky. In addressing this conundrum, Xu et al. observed aberrant 14-3-3ζ expression to prevent the formation of tumor-suppressive Smad2/3:p53 complexes, while simultaneously driving the generation of oncogenic Smad2/3:Gli2 complexes. Once formed, Smad2/3:Gli2 complexes stimulate the expression of parathyroid hormone-related protein necessary for breast cancer metastasis to bone. This viewpoint highlights 14-3-3ζ as an essential driver of oncogenic signaling by Smad2/3 and TGF-β in metastatic breast cancers.
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein Research Building, 2103 Cornell Road, Cleveland, OH, 44106, USA. cdm58@case.edu.
authors.forename: Chevaun D
authors.initials: CD
authors.lastname: Morrison
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein Research Building, 2103 Cornell Road, Cleveland, OH, 44106, USA. wps20@case.edu.
authors.forename: William P
authors.initials: WP
authors.lastname: Schiemann
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D048948:14-3-3 Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53