title: By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy.
abstract: Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which shows that low expression of miR-100 is a negative prognostic factor and is associated with gene signatures of high grade undifferentiated tumors. Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments.
authors.affiliation: University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Petrelli
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Rosachiara
authors.initials: R
authors.lastname: Carollo
authors.affiliation: University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Cargnelutti
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Iovino
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Callari
authors.affiliation: Molecular Biotechnology Center (MBC), Department of Oncological Sciences, Center for Molecular Systems Biology, Via Nizza, University of Torino, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimino
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Laura Rosa
authors.initials: LR
authors.lastname: Mangiapane
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giammona
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cordova
authors.affiliation: University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
authors.affiliation: Molecular Biotechnology Center (MBC), Department of Oncological Sciences, Center for Molecular Systems Biology, Via Nizza, University of Torino, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.affiliation: Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.affiliation: University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology; D014183:Transplantation, Heterologous; D000097869:Polo-Like Kinase 1
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018797:Cell Cycle Proteins; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000097869:Polo-Like Kinase 1; C544266:MIRN100 microRNA, human