ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy

• DOI: 10.18632/oncotarget.15537
• Publication Date: 2017-02-22T16:33:37Z
• Authors: Martina Antonelli; Flavie Strappazzon; Ivan Arisi; Rossella Brandi; Mara D’Onofrio; Manolo Sambucci; Gwenola Manic; Ilio Vitale; Daniela Barilà; Venturina Stagni
• Keywords: 0301 basic medicine; autophagy; ATG4; ATM kinase; autophagy; breast cancer stem cells (BCSCs); mammospheres; Settore BIO/18 - GENETICA; mammosphere; Blotting, Western; Autophagy-Related Proteins; Fluorescent Antibody Technique; Breast Neoplasms; Ataxia Telangiectasia Mutated Proteins; Polymerase Chain Reaction; Cell Line; 12. Responsible consumption; Ataxia Telangiectasia Mutated Protein; 03 medical and health sciences; Cell Line, Tumor; Autophagy; Humans; Oligonucleotide Array Sequence Analysis; Neoplastic; Tumor; Blotting; Oligonucleotide Array Sequence Analysi; ATG4; ATM kinase; autophagy; breast cancer stem cells (BCSCs); mammospheres; Ataxia Telangiectasia Mutated Proteins; Autophagy-Related Proteins; Blotting, Western; Breast Neoplasms; Cell Line, Tumor; Cysteine Endopeptidases; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Humans; Neoplastic Stem Cells; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Autophagy; breast cancer stem cells (BCSCs); 3. Good health; Gene Expression Regulation, Neoplastic; Cysteine Endopeptidases; Gene Expression Regulation; Autophagy-Related Protein; Neoplastic Stem Cells; ATG4; Female; Neoplastic Stem Cell; ATM kinase; Western; Breast Neoplasm; Cysteine Endopeptidase; Human; Research Paper

// Martina Antonelli 1, 2 , Flavie Strappazzon 1 Ivan Arisi 3 Rossella Brandi Mara D'Onofrio Manolo Sambucci 4 Gwenola Manic Ilio Vitale 2, 5 Daniela Barilà Venturina Stagni Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy Department of Biology, University Rome 'Tor Vergata', Genomics Facility, European Brain Research Institute (EBRI) 'Rita Levi-Montalcini', Neuroimmunology Unit, IRCCS, Regina Elena National Cancer Center Institute, Correspondence to: Stagni, email: [e-mail] Barilà, [e-mail] Keywords: ATM kinase, breast cancer stem cells (BCSCs), mammospheres, autophagy, ATG4 Received: July 05, 2016 Accepted: January 23, 2017 Published: February 20, ABSTRACT The efficacy Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in therapy is tempered by the identification new emerging functions ATM, which suggests that role this protein progression complex. We recently demonstrated tumor suppressor gene could act as promoting factor HER2 (Human Epidermal Growth Factor Receptor 2) positive cancer. Herein we put evidence expression sustains proportion with stem-like phenotype, measured capability to form independently levels. Transcriptomic analyses revealed that, modulates cell cycle-, DNA repair- and autophagy-related genes. Among these, silencing autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs mammosphere formation similarly depletion. Conversely, ATG4C ectopic silenced for expression, rescues mammospheres growth. Finally, array analyses, performed using public data, identify significant correlation between levels all human subtypes, except basal-like one. Overall, uncover connection regulation demonstrate cells, are essential drivers formation, suggesting their targeting may improve current approaches eradicate phenotype.