Galectin-3 Interacts with C/EBPβ and Upregulates Hyaluronan-Mediated Motility Receptor Expression in Gastric Cancer

被引：28
作者：
Kang, Hyeon-Gu [1 ,2 ,3 ]
Kim, Won-Jin [1 ,2 ,3 ]
Kang, Hyeok-Gu [4 ,5 ]
Chun, Kyung-Hee [4 ,5 ]
Kim, Seok-Jun [1 ,2 ,3 ]
机构：
[1] Chosun Univ, Coll Nat Sci, Dept Biomed Sci, Gwangju 61452, South Korea
[2] Chosun Univ, Dept Life Sci, Gwangju, South Korea
[3] Chosun Univ, Brain Korea 21 Plus Res Team Bioact Control Techn, Gwangju, South Korea
[4] Yonsei Univ, Dept Biochem & Mol Biol, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea
[5] Yonsei Univ, Brain Korea 21 Plus Project Med Sci, Coll Med, Seoul, South Korea
来源：
MOLECULAR CANCER RESEARCH | 2020年 / 18卷 / 03期
基金：
新加坡国家研究基金会;
关键词：
TARGETED THERAPY; METASTASIS; CELLS; RHAMM;
D O I：
10.1158/1541-7786.MCR-19-0811
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The hyaluronan-mediated motility receptor (HMMR) is over-expressed in gastric cancer; however, the apparent role of HMMR has not been well defined owing to lack of detailed studies on gastric tumorigenesis. Therefore, we elucidated the functional and regulatory mechanisms of HMMR in gastric cancer. Using publicly available data, we confirmed HMMR overexpression in patients with gastric cancer. HMMR silencing decreased proliferation, migration, and invasion of gastric cancer cells, whereas HMMR overexpression reversed these effects. A gastric cancer xenograft mouse model showed statistically significant inhibition of tumor growth upon HMMR depletion. Previous data from cDNA microarray showed reduced HMMR expression upon inhibition of galectin-3. However, overexpression of galectin-3 increased HMMR expression, cell proliferation, and motility in gastric cancer cells, whereas HMMR silencing blocked these effects. Interestingly, galectin-3 interacted directly with C/EBP beta and bound to HMMR promoter to drive its transcription, and gastric cancer cell proliferation and motility. Altogether, high expression of HMMR promoted gastric cancer cell proliferation and motility and could be a prognostic factor in gastric cancer. In addition, HMMR expression was regulated by the interaction between C/EBP beta and galectin-3. Therefore, targeting HMMR along with galectin-3 and C/EBPb complex could be a potential treatment strategy for inhibiting gastric cancer progression and metastasis.
引用
收藏
页码：403 / 413
页数：11
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