title: CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer.
abstract: Carbonic anhydrase IX(CA9)is a member of the carbonic anhydrase family that catalyzes the reversible hydration of carbon dioxide, and plays a key role in the regulation of pH. Although a large number of studies have shown that CA9 is strongly up-regulated by HIF1-α, little is known about the negative regulation mechanism of CA9 in cancer cells. Here we find that CREB is a key negative regulator of CA9 in gastric cancer. Over-expression of CREB can significantly repress the expression of CA9. Treating with anisomycin (ANS), an activator of p38, the phosphorylation and nuclear translocation of CREB are both promoted, while the transcription of CA9 is repressed. Besides, our results firstly identify that CREB can recruit SIRT1 (class III HDACS) by adaptor protein p300, then repress the expression of CA9. These findings may contribute to understand the negative regulation mechanisms of CA9 in gastric cancer.
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
authors.forename: Guanqiao
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Funan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China. Electronic address: fli@mail.cmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D014183:Transplantation, Heterologous; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000841:Anisomycin; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050880:p300-CBP Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: CA9; CREB; Gastric cancer; Proliferation; SIRT1