title: Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas.
abstract: Many solid cancers have an expanded CD44+/hi/CD24-/lowcancer stem cell (CSC) population, which are relatively chemoresistant and drive recurrence and metastasis. Achieving a more durable response requires the development of therapies that specifically target CSCs. Recent evidence indicated that inhibiting the SUMO pathway repressed tumor growth and invasiveness, although the mechanism has yet to be clarified. Here, we demonstrate that inhibition of the SUMO pathway repressed MMP14 and CD44 with a concomitant reduction in cell invasiveness and functional loss of CSCs in basal breast cancer. Similar effects were demonstrated with a panel of E1 and E3 SUMO inhibitors. Identical results were obtained in a colorectal cancer cell line and primary colon cancer cells. In both breast and colon cancer, SUMO-unconjugated TFAP2A mediated the effects of SUMO inhibition. These data support the development of SUMO inhibitors as an approach to specifically target the CSC population in breast and colorectal cancer.
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Bogachek
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Jung M
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: De Andrade
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Allison W
authors.initials: AW
authors.lastname: Lorenzen
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Kulak
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: White
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Vivian W
authors.initials: VW
authors.lastname: Gu
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Wu
authors.affiliation: Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA. Electronic address: ronald-weigel@uiowa.edu.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Weigel
mesh_terms: D048729:Anacardic Acids / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D048729:Anacardic Acids; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D025841:Small Ubiquitin-Related Modifier Proteins; C088115:anacardic acid; D053511:Matrix Metalloproteinase 14
keywords: CD44; MMP14; TFAP2A; breast cancer; cancer stem cell; colon cancer; sumoylation