title: Upregulation of SMAD4 by MZF1 inhibits migration of human gastric cancer cells.
abstract: SMAD4 is a tumor suppressor that is frequently inactivated in many types of cancer. The role of abnormal expression of SMAD4 has been reported in developmental processes and the progression of various human cancers. The expression level of SMAD4 has been related to the survival rate in gastric cancer patients. However, the molecular mechanism underlying transcriptional regulation of SMAD4 remains largely unknown. In the present study, we characterized the promoter region of SMAD4 and identified myeloid zinc finger 1 (MZF1), as a putative transcription factor. MZF1 directly bound to a core region of the SMAD4 promoter and stimulated transcriptional activity. We also found that the expression of MZF1 influences the migration ability of gastric adenocarcinoma cells. Collectively, our results showed that MZF1 has a role in cellular migration of gastric cancer cells via promoting an increase in intracellular SMAD4 levels. This study might provide new evidence for the molecular basis of the tumor suppressive effect of the MZF1-SMAD4 axis, a new therapeutic target in advanced human gastric cancer.
authors.affiliation: Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hun Seok
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.affiliation: Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Rajasekaran
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, P.R. China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Microbiology, College of Pharmacy, Catholic University, Daegu, Republic of Korea.
authors.forename: Joon-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051901:Smad4 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; C497796:SMAD4 protein, human; D051901:Smad4 Protein