Open AccessComplex roles of the actin‐binding protein Girdin/GIV in DNA damage‐induced apoptosis of cancer cells
Author(s) -
Chen Chen,
Enomoto Atsushi,
Weng Liang,
Taki Tetsuro,
Shiraki Yukihiro,
Mii Shinji,
Ichihara Ryosuke,
Kanda Mitsuro,
Koike Masahiko,
Kodera Yasuhiro,
Takahashi Masahide
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14637
Subject(s) - biology , dna damage , apoptosis , hela , cell cycle , cancer cell , microbiology and biotechnology , cancer , cancer research , cell growth , cell , dna , genetics
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 G 1 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.