title: TAp63 suppresses mammary tumorigenesis through regulation of the Hippo pathway.
abstract: Mechanisms regulating the transition of mammary epithelial cells (MECs) to mammary stem cells (MaSCs) and to tumor-initiating cells (TICs) have not been entirely elucidated. The p53 family member, p63, is critical for mammary gland development and contains transactivation domain isoforms, which have tumor-suppressive activities, and the ΔN isoforms, which act as oncogenes. In the clinic, p63 is often used as a diagnostic marker, and further analysis of the function of TAp63 in the mammary gland is critical for improved diagnosis and patient care. Loss of TAp63 in mice leads to the formation of aggressive metastatic mammary adenocarcinoma at 9-16 months of age. Here we show that TAp63 is crucial for the transition of mammary cancer cells to TICs. When TAp63 is lost, MECs express embryonic and MaSC signatures and activate the Hippo pathway. These data indicate a crucial role for TAp63 in mammary TICs and provide a mechanism for its role as a tumor- and metastasis-suppressor in breast cancer.
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Napoli
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Abbas
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.|Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Venkatanarayan
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.|Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: N H B
authors.initials: NHB
authors.lastname: Bui
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Coarfa
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Gi
authors.affiliation: Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Kittrell
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Gunaratne
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Medina
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rosen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: F
authors.initials: F
authors.lastname: Behbod
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Houston, Tampa, FL, USA.|Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Flores
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D063646:Carcinogenesis; D002452:Cell Count; D045744:Cell Line, Tumor; D016764:Cell Polarity; D002471:Cell Transformation, Neoplastic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D000090683:Hippo Signaling Pathway; D006801:Humans; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases