Your browser doesn't support javascript.
loading
Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response.
Amin, Ruhul; Shukla, Anjali; Zhu, Jacqueline Jufen; Kim, Sohyoung; Wang, Ping; Tian, Simon Zhongyuan; Tran, Andy D; Paul, Debasish; Cappell, Steven D; Burkett, Sandra; Liu, Huaitian; Lee, Maxwell P; Kruhlak, Michael J; Dwyer, Jennifer E; Simpson, R Mark; Hager, Gordon L; Ruan, Yijun; Hunter, Kent W.
Afiliação
  • Amin R; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA. ruhul.amin@nih.gov.
  • Shukla A; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Zhu JJ; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Kim S; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Wang P; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Tian SZ; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Tran AD; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Paul D; Confocal Microscopy Core Facility, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Cappell SD; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Burkett S; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Liu H; Molecular Cytogenetics Core Facility, National Cancer Institute, NIH, Frederick, MD, USA.
  • Lee MP; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Kruhlak MJ; High-Dimension Data Analysis Group, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Dwyer JE; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Simpson RM; High-Dimension Data Analysis Group, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Hager GL; Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Ruan Y; Confocal Microscopy Core Facility, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Hunter KW; Molecular Pathology Unit, Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Nat Commun ; 12(1): 7216, 2021 12 13.
Article em En | MEDLINE | ID: mdl-34903738
ABSTRACT
Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Heterocromatina / Complexo de Proteínas Formadoras de Poros Nucleares / Mecanotransdução Celular Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Heterocromatina / Complexo de Proteínas Formadoras de Poros Nucleares / Mecanotransdução Celular Idioma: En Ano de publicação: 2021 Tipo de documento: Article