Cargando…
PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells
Poly- adenosine diphosphate (ADP)-ribose (PAR) is a polymer synthesized as a posttranslational modification by some poly (ADP-ribose) polymerases (PARPs), namely PARP-1, PARP-2, tankyrase-1, and tankyrase-2 (TNKS-1/2). PARP-1 is nuclear and has also been detected in extracellular vesicles. PARP-2 an...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387051/ https://www.ncbi.nlm.nih.gov/pubmed/30691122 http://dx.doi.org/10.3390/ijms20030518 |
_version_ | 1783397484190498816 |
---|---|
author | Schacke, Michelle Kumar, Janani Colwell, Nicholas Hermanson, Kole Folle, Gustavo A. Nechaev, Sergei Dhasarathy, Archana Lafon-Hughes, Laura |
author_facet | Schacke, Michelle Kumar, Janani Colwell, Nicholas Hermanson, Kole Folle, Gustavo A. Nechaev, Sergei Dhasarathy, Archana Lafon-Hughes, Laura |
author_sort | Schacke, Michelle |
collection | PubMed |
description | Poly- adenosine diphosphate (ADP)-ribose (PAR) is a polymer synthesized as a posttranslational modification by some poly (ADP-ribose) polymerases (PARPs), namely PARP-1, PARP-2, tankyrase-1, and tankyrase-2 (TNKS-1/2). PARP-1 is nuclear and has also been detected in extracellular vesicles. PARP-2 and TNKS-1/2 are distributed in nuclei and cytoplasm. PARP or PAR alterations have been described in tumors, and in particular by influencing the Epithelial- Mesenchymal Transition (EMT), which influences cell migration and drug resistance in cancer cells. Pro-EMT and anti-EMT effects of PARP-1 have been reported while whether PAR changes occur specifically during EMT is currently unknown. The PARP-1/2 inhibitor Olaparib (OLA) is approved by FDA to treat certain patients harboring cancers with impaired homologous recombination. Here, we studied PAR changes and OLA effects on EMT. Total and nuclear PAR increased in EMT while PAR belts were disassembled. OLA prevented EMT, according to: (i) molecular markers evaluated by immuno-cytofluorescence/image quantification, Western blots, and RNA quantitation, (ii) morphological changes expressed as anisotropy, and (iii) migration capacity in the scratch assay. OLA also partially reversed EMT. OLA might work through unconventional mechanisms of action (different from synthetic lethality), even in non-BRCA (breast cancer 1 gene) mutated cancers. |
format | Online Article Text |
id | pubmed-6387051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63870512019-02-27 PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells Schacke, Michelle Kumar, Janani Colwell, Nicholas Hermanson, Kole Folle, Gustavo A. Nechaev, Sergei Dhasarathy, Archana Lafon-Hughes, Laura Int J Mol Sci Article Poly- adenosine diphosphate (ADP)-ribose (PAR) is a polymer synthesized as a posttranslational modification by some poly (ADP-ribose) polymerases (PARPs), namely PARP-1, PARP-2, tankyrase-1, and tankyrase-2 (TNKS-1/2). PARP-1 is nuclear and has also been detected in extracellular vesicles. PARP-2 and TNKS-1/2 are distributed in nuclei and cytoplasm. PARP or PAR alterations have been described in tumors, and in particular by influencing the Epithelial- Mesenchymal Transition (EMT), which influences cell migration and drug resistance in cancer cells. Pro-EMT and anti-EMT effects of PARP-1 have been reported while whether PAR changes occur specifically during EMT is currently unknown. The PARP-1/2 inhibitor Olaparib (OLA) is approved by FDA to treat certain patients harboring cancers with impaired homologous recombination. Here, we studied PAR changes and OLA effects on EMT. Total and nuclear PAR increased in EMT while PAR belts were disassembled. OLA prevented EMT, according to: (i) molecular markers evaluated by immuno-cytofluorescence/image quantification, Western blots, and RNA quantitation, (ii) morphological changes expressed as anisotropy, and (iii) migration capacity in the scratch assay. OLA also partially reversed EMT. OLA might work through unconventional mechanisms of action (different from synthetic lethality), even in non-BRCA (breast cancer 1 gene) mutated cancers. MDPI 2019-01-26 /pmc/articles/PMC6387051/ /pubmed/30691122 http://dx.doi.org/10.3390/ijms20030518 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Schacke, Michelle Kumar, Janani Colwell, Nicholas Hermanson, Kole Folle, Gustavo A. Nechaev, Sergei Dhasarathy, Archana Lafon-Hughes, Laura PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells |
title | PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells |
title_full | PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells |
title_fullStr | PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells |
title_full_unstemmed | PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells |
title_short | PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-β in NMuMG Cells |
title_sort | parp-1/2 inhibitor olaparib prevents or partially reverts emt induced by tgf-β in nmumg cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387051/ https://www.ncbi.nlm.nih.gov/pubmed/30691122 http://dx.doi.org/10.3390/ijms20030518 |
work_keys_str_mv | AT schackemichelle parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT kumarjanani parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT colwellnicholas parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT hermansonkole parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT follegustavoa parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT nechaevsergei parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT dhasarathyarchana parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells AT lafonhugheslaura parp12inhibitorolaparibpreventsorpartiallyrevertsemtinducedbytgfbinnmumgcells |