CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer

Guanqiao Wang; Zhenguo Cheng; Funan Liu; Hongyan Zhang; Jiabin Li; Feng Li

doi:10.1016/j.cellsig.2015.03.019

CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer

Cell Signal. 2015 Jul;27(7):1369-79. doi: 10.1016/j.cellsig.2015.03.019. Epub 2015 Apr 2.

Authors

Guanqiao Wang¹, Zhenguo Cheng¹, Funan Liu², Hongyan Zhang¹, Jiabin Li¹, Feng Li³

Affiliations

¹ 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.
² Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
³ 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.

PMID: 25843777
DOI: 10.1016/j.cellsig.2015.03.019

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.

Keywords: CA9; CREB; Gastric cancer; Proliferation; SIRT1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anisomycin / pharmacology
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism*
CREB-Binding Protein / metabolism*
Carbonic Anhydrase IX
Carbonic Anhydrases / genetics
Carbonic Anhydrases / metabolism*
Cell Line, Tumor
Down-Regulation
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Phosphorylation / drug effects
Promoter Regions, Genetic
Protein Synthesis Inhibitors / pharmacology
RNA, Messenger / metabolism
Sirtuin 1 / metabolism
Stomach Neoplasms / enzymology*
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Transcription, Genetic / drug effects
Transplantation, Heterologous
p300-CBP Transcription Factors / metabolism
p38 Mitogen-Activated Protein Kinases / chemistry
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Antigens, Neoplasm
Hypoxia-Inducible Factor 1, alpha Subunit
Protein Synthesis Inhibitors
RNA, Messenger
Anisomycin
CREB-Binding Protein
CREBBP protein, human
p300-CBP Transcription Factors
p38 Mitogen-Activated Protein Kinases
SIRT1 protein, human
Sirtuin 1
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases