CXXC4 activates apoptosis through up-regulating GDF15 in gastric cancer
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Mengjiao Han1, Dongjun Dai1, Neelum Aziz Yousafzai1, Faliang Wang2, Hanying Wang1, Qiying Zhou1, Haiqi Lu1, Wenxia Xu2, Lifeng Feng2, Hongchuan Jin2 and Xian Wang1
1Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China
2Labortaory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China
Xian Wang, email: [email protected]
Keywords: CXXC4, GDF15, apoptosis, gastric cancer
Received: June 30, 2017 Accepted: September 05, 2017 Published: October 06, 2017
Worldwide, gastric cancer is one of the most fatal cancers. Epigenetic alterations in gastric cancer play important roles in silencing of tumor suppressor genes. We previously found that CXXC finger protein 4 (CXXC4) was a novel tumor suppressor in gastric cancer. In this report, we demonstrated that CXXC4 inhibited growth of gastric cancer cells as a pro-apoptotic factor. This inhibition could be reversed by the pan-caspase inhibitor called Z-VAD-FMK. However, CXXC4 with mutations in its DNA binding domain failed to induce apoptosis. Growth differentiation factor 15 (GDF15) was identified as one of potential targets responsible for CXXC4-induced apoptosis. CXXC4 activated GDF15 transcription through enhancing the interaction of transcription factor Sp1 with GDF15 promoter. In summary, the nuclear protein CXXC4 activated apoptosis in gastric cancer through up-regulating its novel potential downstream target GDF15. GDF15 might be a promising target for clinical treatment of gastric cancer with CXXC4 deficiency.
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