Complex roles of the actin-binding protein Girdin/GIV in DNA damage-induced apoptosis of cancer cells

Chen Chen, Atsushi Enomoto, Liang Weng, Tetsuro Taki, Yukihiro Shiraki, Shinji Mii, Ryosuke Ichihara, Mitsuro Kanda, Masahiko Koike, Yasuhiro Kodera, Masahide Takahashi

研究成果: Article査読

抄録

The actin-binding protein Girdin is a hub protein that interacts with multiple proteins to regulate motility and Akt and trimeric G protein signaling in cancer cells. Girdin expression correlates with poor outcomes in multiple human cancers. However, those findings are not universal, as they depend on study conditions. Those data suggest that multiple aspects of Girdin function and its role in tumor cell responses to anticancer therapeutics must be reconsidered. In the present study, we found that Girdin is involved in DNA damage-induced cancer cell apoptosis. An esophageal cancer cell line that exhibited high Girdin expression showed a marked sensitivity to UV-mediated DNA damage compared to a line with low Girdin expression. When transcriptional activation of endogenous Girdin was mediated by an engineered CRISPR/Cas9 activation system, sensitivity to DNA damage increased in both stationary and migrating HeLa cancer cells. High Girdin expression was associated with dysregulated cell cycle progression and prolonged G1 and M phases. These features were accompanied by p53 activation, which conceivably increases cancer cell vulnerability to UV exposure. These data highlight the importance of understanding complex Girdin functions that influence cancer cell sensitivity to therapeutics.

本文言語English
ページ(範囲)4303-4317
ページ数15
ジャーナルCancer science
111
11
DOI
出版ステータスPublished - 01-11-2020

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

フィンガープリント

「Complex roles of the actin-binding protein Girdin/GIV in DNA damage-induced apoptosis of cancer cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル