title: The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype.
abstract: Triple-negative breast cancer (TNBC) is a very aggressive type of tumour and its aggressiveness is linked to E-cadherin downregulation. In estrogen-sensitive breast cancer, high levels of E-cadherin fit with high levels of ERα and MTA3 (a component of the transcription Mi-2/NuRD complex with intrinsic DAC activity). In TNBC the E-cadherin downregulation could be due to epigenetic silencing of the CDH1 gene as well as to the lack of a fully functioning ERα-activated pathway. We report that the pan-histone deacetylase inhibitor LBH589, a potent anti-proliferative agent, induced E-cadherin expression on cell membranes of MDA-MB-231 cells (TNBC), determining a reduction of cell invasion and migration. Even though E-cadherin expression in breast cancer is also regulated by estradiol and the ERα/MTA3/Snail/Slug pathway, LBH589 is able to increase E-cadherin without affecting the estrogen pathway. In fact, no expression of ERα, PR and FoxA1 was observed in MDA-MB-231 cells before and after LBH589 treatment; furthermore, the drug caused an increase in Snail and Slug expression with a concomitant reduction of MTA3 levels. Taking into consideration its anti-proliferative and anti-invasive properties, we suggest the use of LBH589 in aggressive breast cancer refractory to hormonal therapy.
authors.affiliation: Oncological Endocrinology, AO Città della Salute e della Scienza di Torino, University of Turin, I-10126 Torino, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Fortunati
authors.affiliation: Department of Medical Sciences, University of Turin, I-10126 Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Marano
authors.affiliation: Department of Oncology, Biochemistry Section, University of Turin, I-10100 Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bandino
authors.affiliation: Department of Medical Sciences, University of Turin, I-10126 Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frairia
authors.affiliation: Department of Medical Sciences, University of Turin, I-10126 Torino, Italy.
authors.forename: Maria Graziella
authors.initials: MG
authors.lastname: Catalano
authors.affiliation: Department of Medical Sciences, University of Turin, I-10126 Torino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boccuzzi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D004958:Estradiol; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D000077767:Panobinostat
chemical_list: D015820:Cadherins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D004958:Estradiol; D000077767:Panobinostat