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Zhao S, Tang H, Yan D, Fan J, Sun H, Wen Y, Yu F, Cui F, Zhang D, Xue Y, Liu C, Yue B, Chen J, Wang J, Wang X, Zhang M, Yu Y, Jiang W, Liu X, Mi Y, Zhou Z, Qin X, Peng Z
DDA1 promotes stage IIB-IIC colon cancer progression by activating NFkappaB/CSN2/GSK-3beta signaling
Oncotarget (2016) 7:19794-812.
Conventional high-recurrence risk factors are not sufficient to predict post-operative risk of tumor recurrence or sensitivity to 5-fluorouracil (5-FU)-based chemotherapy for stage II colon cancer. DDA1, an evolutionarily conserved gene located at 19p13.11, may be involved in the activation of nuclear factor kappaB (NFkappaB). This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of stage II colon cancer via activation of the NFkappaB pathway. We found that positive expression of DDA1 alone or in combination with p65 nuclear translocation correlated with increased risk of tumor recurrence in patients with stage IIB-IIC colon cancer. DDA1 overexpression in colon cancer lines promoted cell proliferation, facilitated cell cycle progression, inhibited 5-FU-induced apoptosis, enhanced invasion, and induced the epithelial-mesenchymal transition. Suppression of DDA1 inhibited tumor progression, and reduced tumor growth in vivo. We also demonstrated that DDA1-mediated tumor progression is associated with the activation of the NFkappaB/COP9 signalosome 2(CSN2)/glycogen synthase kinase3beta (GSK3beta) pathway. These results indicate that DDA1 promotes colon cancer progression through activation of NFkappaB/CSN2/GSK3beta signaling. DDA1, together with NFkappaB activation status, may serve as a sensitive biomarker for tumor recurrence risk and prognosis in patients with stage IIB-IIC colon cancers.
Publication Date: 2016-04-12.
PMCID: PMC4991419
Last updated on Saturday, August 22, 2020