title: Senescence-associated secretory phenotype favors the emergence of cancer stem-like cells.
abstract: The molecular mechanisms underlying cancer resistance remain elusive. One possible explanation is that cancer stem cells (CSCs) elude drug treatment, emerge and reproduce a tumor. Using multiple myeloma as a paradigm, we showed that cancer stem-like cells (CSLCs) appear after genotoxic stress because of their intrinsic properties. However, these properties do not drive the emergence of the CSLCs. Following genotoxic stress, remaining DNA damages lead to a senescence-associated secretory phenotype (SASP). Senescent cells, which are the non-CSLCs, secrete chemokines contributing to the emergence, maintenance and migration of CSLCs. Downregulation of checkpoint protein 2, a key player of SASP, significantly reduced the emergence of CSLCs. Our results unravel a novel molecular mechanism by which SASP might promote malignancy, underlining the dual role of senescence in tumorigenesis. This mechanism, based on mutual cooperation among tumor cells, illustrates how cancer may relapse; its targeting could represent new therapeutic opportunities.
authors.affiliation: MILPAT (EA 4652), Faculté de Médecine, Université de Caen Basse-Normandie, CHU Côte de Nacre, Caen, France. julie.cahu@gmail.com
authors.forename: J
authors.initials: J
authors.lastname: Cahu
authors.forename: S
authors.initials: S
authors.lastname: Bustany
authors.forename: B
authors.initials: B
authors.lastname: Sola
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D016922:Cellular Senescence; D064447:Checkpoint Kinase 2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport
chemical_list: D018925:Chemokines; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases