title: ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.
abstract: Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ΔNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Rumela
authors.initials: R
authors.lastname: Chakrabarti
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hang
authors.affiliation: 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Andres Blanco
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Abrar
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tiede
authors.affiliation: Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York 14203, USA.
authors.forename: Rose-Anne
authors.initials: RA
authors.lastname: Romano
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: DeCoste
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mercatali
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Kannan
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
authors.affiliation: Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York 14203, USA.
authors.forename: Satrajit
authors.initials: S
authors.lastname: Sinha
authors.affiliation: 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C115810:FZD7 protein, human; D051157:Frizzled Receptors; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins