title: RB1 and p53 at the crossroad of EMT and triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is a heterogeneous disease that includes Basal-like and Claudin-low tumors. The Claudin-low tumors are enriched for features associated with epithelial-to-mesenchymal transition (EMT) and possibly for tumor initiating cells. Primary TNBCs respond relatively well to conventional chemotherapy; however, metastatic disease is virtually incurable. Thus, there is a great interest in identifying specific therapeutic targets for TNBC. The tumor suppressor RB1 is frequently lost in Basal-like breast cancer. To test for a causative role of RB1 gene loss in BC and for its effect on specific subtypes, we deleted mouse Rb in mammary stem/bipotent progenitor cells. This led to diverse mammary tumors including TNBC, with a subset of the latter containing p53 mutations and exhibiting features of Basal-like BC or EMT. Combined mutation of Rb and p53 in mammary stem/bipotent progenitors induced EMT type tumors. Here, we review our findings and those of others, which connect Rb and p53 to EMT in TNBC. Furthermore, we discuss how by understanding this circuit and its vulnerabilities, we may identify novel therapy for TNBC.
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jiang
authors.forename: Robert
authors.initials: R
authors.lastname: Jones
authors.forename: Jeff C
authors.initials: JC
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Deng
authors.forename: Tyler
authors.initials: T
authors.lastname: Robinson
authors.forename: Philip E D
authors.initials: PE
authors.lastname: Chung
authors.forename: Sharon
authors.initials: S
authors.lastname: Wang
authors.forename: Jason I
authors.initials: JI
authors.lastname: Herschkowitz
authors.forename: Sean E
authors.initials: SE
authors.lastname: Egan
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Eldad
authors.initials: E
authors.lastname: Zacksenhaus
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53