Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis.
Identification of precise prognostic marker and effective therapeutic target is pivotal in the treatment of gastric cancer. In the present study, we determined the level of RUNX3 expression in gastric cancer cells and gastric cancer specimens and the impact of its alteration on cancer biology and clinical outcome. There was a loss or substantial decrease of RUNX3 protein expression in 86 cases of gastric tumors as compared with that in normal gastric mucosa (P < 0.0001), which was significantly associated with inferior survival duration (P = 0.0005). In a Cox proportional hazards model, RUNX3 expression independently predicted better survival (P = 0.036). Moreover, various human gastric cancer cell lines also exhibited loss or drastic decrease of RUNX3 expression. Enforced restoration of RUNX3 expression led to down-regulation of cyclin D1 but to up-regulation of p27, caspase 3, 7, and 8 expression, cell cycle arrest, and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer.
Wei
Daoyan
D
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gong
Weida
W
Oh
Sang C
SC
Li
Qiang
Q
Kim
Won Dong
WD
Wang
Liwei
L
Le
Xiangdong
X
Yao
James
J
Wu
Tsung T
TT
Huang
Suyun
S
Xie
Keping
K
D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D050677:Core Binding Factor Alpha 3 Subunit; D019938:Cyclin D1 / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C493729:Runx3 protein, human; D014157:Transcription Factors; D019938:Cyclin D1; D020169:Caspases