title: Loss of Chromosome 8p Governs Tumor Progression and Drug Response by Altering Lipid Metabolism.
abstract: Large-scale heterozygous deletions are a hallmark of cancer genomes. The concomitant loss of multiple genes creates vulnerabilities that are impossible to reveal through the study of individual genes. To delineate the functional outcome of chromosome 8p loss of heterozygosity (LOH), a common aberration in breast cancer, we modeled 8p LOH using TALEN-based genomic engineering. 8p LOH alters fatty acid and ceramide metabolism. The shift in lipid metabolism triggers invasiveness and confers tumor growth under stress conditions due to increased autophagy. The resistance of 8p-deleted cells to chemotherapeutic drugs concurs with poorer survival rates of breast cancer patients harboring an 8p LOH. The autophagy dependency of 8p-deleted cells provides the rational basis for treatment of 8p LOH tumors with autophagy inhibitors.
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Crowther
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Tibor
authors.initials: T
authors.lastname: Pastor
authors.affiliation: Department of Oncology, KU Leuven, Leuven 3000, Belgium.
authors.forename: Layka
authors.initials: L
authors.lastname: Abbasi Asbagh
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Baietti
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Magdalena
authors.initials: M
authors.lastname: De Troyer
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Iria
authors.initials: I
authors.lastname: Vazquez
authors.affiliation: Department of Oncology, KU Leuven, Leuven 3000, Belgium.
authors.forename: Ali
authors.initials: A
authors.lastname: Talebi
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Renzi
authors.affiliation: Department of Oncology, KU Leuven, Leuven 3000, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Dehairs
authors.affiliation: Department of Oncology, KU Leuven, Leuven 3000, Belgium.
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.affiliation: VIB Center for the Biology of Disease, VIB, Leuven 3000, Belgium; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium. Electronic address: anna.sablina@cme.vib-kuleuven.be.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Sablina
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D053208:Kaplan-Meier Estimate; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D015999:Multivariate Analysis; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents