論文

査読有り 本文へのリンクあり
2019年1月

Palbociclib enhances activin-SMAD-induced cytostasis in estrogen receptor-positive breast cancer

Cancer Science
  • Mayumi Harada
  • ,
  • Masato Morikawa
  • ,
  • Takayuki Ozawa
  • ,
  • Mai Kobayashi
  • ,
  • Yusuke Tamura
  • ,
  • Kei Takahashi
  • ,
  • Masahiko Tanabe
  • ,
  • Keiichiro Tada
  • ,
  • Yasuyuki Seto
  • ,
  • Kohei Miyazono
  • ,
  • Daizo Koinuma

110
1
開始ページ
209
終了ページ
220
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.13841

Cyclin-dependent kinase (CDK) 4 and CDK6 inhibitors are effective therapeutic options for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about the clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor palbociclib and activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Palbociclib enhanced SMAD2 binding to the genome by inhibiting CDK4/6-mediated linker phosphorylation of the SMAD2 protein. We also showed that cyclin G2 plays essential roles in SMAD2-dependent cytostatic response. Moreover, comparison of the SMAD2 ChIP-seq data of T47D cells with those of Hs578T (triple-negative breast cancer cells) indicated that palbociclib augmented different SMAD2-mediated functions based on cell type, and enhanced SMAD2 binding to the target regions on the genome without affecting its binding pattern. In summary, palbociclib enhances the cytostatic effects of the activin-SMAD2 signaling pathway, whereas it possibly strengthens the tumor-promoting aspect in aggressive breast cancer.

リンク情報
DOI
https://doi.org/10.1111/cas.13841
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30343527
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056661448&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85056661448&origin=inward
ID情報
  • DOI : 10.1111/cas.13841
  • ISSN : 1347-9032
  • eISSN : 1349-7006
  • PubMed ID : 30343527
  • SCOPUS ID : 85056661448

エクスポート
BibTeX RIS