@Article{or.2022.03529,
AUTHOR = {BIN LIU, HAIPENG LIU, FEIFEI REN, HANGFAN LIU, IHTISHAM BUKHARI, YUMING FU, WANQING WU, MINGHAI ZHAO, SHAOGONG ZHU, HUI MO, FAZHAN LI, MICHAEL B. ZHENG, YOUCAI TANG, PENGYUAN ZHENG, YANG MI},
TITLE = {cGAS regulates the DNA damage response to maintain proliferative signaling in gastric cancer cells},
JOURNAL = {Oncology Research},
VOLUME = {29},
YEAR = {2021},
NUMBER = {2},
PAGES = {87--103},
URL = {http://www.techscience.com/or/v29n2/48799},
ISSN = {1555-3906},
ABSTRACT = {The activation of some oncogenes promote cancer cell proliferation and growth, facilitate cancer progression
and metastasis by induce DNA replication stress, even genome instability. Activation of the cyclic GMP-AMP synthase
(cGAS) mediates classical DNA sensing, is involved in genome instability, and is linked to various tumor development or
therapy. However, the function of cGAS in gastric cancer remains elusive. In this study, the TCGA database and
retrospective immunohistochemical analyses revealed substantially high cGAS expression in gastric cancer tissues and
cell lines. By employing cGAS high-expression gastric cancer cell lines, including AGS and MKN45, ectopic silencing
of cGAS caused a significant reduction in the proliferation of the cells, tumor growth, and mass in xenograft mice.
Mechanistically, database analysis predicted a possible involvement of cGAS in the DNA damage response (DDR),
further data through cells revealed protein interactions of the cGAS and MRE11-RAD50-NBN (MRN) complex,
which activated cell cycle checkpoints, even increased genome instability in gastric cancer cells, thereby contributing
to gastric cancer progression and sensitivity to treatment with DNA damaging agents. Furthermore, the upregulation
of cGAS significantly exacerbated the prognosis of gastric cancer patients while improving radiotherapeutic outcomes.
Therefore, we concluded that cGAS is involved in gastric cancer progression by fueling genome instability, implying
that intervening in the cGAS pathway could be a practicable therapeutic approach for gastric cancer.},
DOI = {10.32604/or.2022.03529}
}