FoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasion

Persistent Link:
http://hdl.handle.net/10150/610293
Title:
FoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasion
Author:
Zheng, Yun; Guo, Jinjun; Zhou, Jin; Lu, Jinjian; Chen, Qi; Zhang, Cui; Qing, Chen; Koeffler, H. Philip; Tong, Yunguang
Affiliation:
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine; Sun Yat-sen University Cancer Center ; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine; Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University; Division of Epidemiology and Biostatistics, College of Public Health, University of Arizona; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau; Department of Pathology, Xinxiang Medical University; School of Pharmaceutical Science, Kunming Medical University
Issue Date:
2015
Publisher:
BioMed Central Ltd
Citation:
Zheng et al. BMC Medical Genomics (2015) 8:49 DOI 10.1186/s12920-015-0126-9
Journal:
BMC Medical Genomics
Rights:
© 2015 Zheng et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND: Metastasis is the major cause of cancer-related death. Forkhead Box M1 (FoxM1) is a master regulator of tumor metastasis. This study aims to identify new FoxM1 targets in regulating tumor metastasis using bioinformatics tools as well as biological experiments. METHODS: Illumina microarray was used to profile WT and PTTG1 knockout HCT116 cells. R2 Genomics Analysis was used to identify PTTG1 as a potential FoxM1 targeted gene. Luciferase reporter array, EMSA and Chromatin Immunoprecipitation (ChIP) were used to determine the binding of FoxM1 to PTTG1 promoter. Boyden chamber assay was used to evaluate the effects of FoxM1-PTTG1 on cell migration and invasion. Splenic-injection induced liver metastasis model was used to evaluate the effects of FoxM1-PTTG1 on liver metastasis of colorectal cancer. RESULTS: Analyses of multiple microarray datasets derived from human colorectal cancer indicated that correlation levels of FoxM1 and pituitary tumor transforming gene (PTTG1) are highly concordant (R = 0.68 ~ 0.89, p = 2.1E-226 ~ 9.6E-86). FoxM1 over-expression increased and knock-down decreased PTTG1 expression. Luciferase reporter assay identified that the −600 to −300 bp region of PTTG1 promoter is important for FoxM1 to enhance PTTG1 promoter activity. EMSA and ChIP assays confirmed that FoxM1 directly binds to PTTG1 promoter at the −391 to −385 bp region in colorectal cancer cells. Boyden chamber assay indicated that both FoxM1 and PTTG1 regulate migration and invasion of HCT116 and SW620 colorectal cancer cells. Further in vivo assays indicated that PTTG1 knock out decreased the liver metastasis of FoxM1 over-expressing HCT116 cells. Microarray analyses identified 662 genes (FDR < 0.05) differentially expressed between WT and PTTG1−/− HCT116 cells. Among them, dickkopf homolog 1 (DKK1), a known WNT pathway inhibitor, was suppressed by PTTG1 and FoxM1. CONCLUSIONS: PTTG1 is a FoxM1 targeted gene. FoxM1 binds to PTTG1 promoter to enhance PTTG1 transcription, and FoxM1-PTTG1 pathway promotes colorectal cancer migration and invasion.
EISSN:
1755-8794
DOI:
10.1186/s12920-015-0126-9
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1755-8794/8/49

Full metadata record

DC FieldValue Language
dc.contributor.authorZheng, Yunen
dc.contributor.authorGuo, Jinjunen
dc.contributor.authorZhou, Jinen
dc.contributor.authorLu, Jinjianen
dc.contributor.authorChen, Qien
dc.contributor.authorZhang, Cuien
dc.contributor.authorQing, Chenen
dc.contributor.authorKoeffler, H. Philipen
dc.contributor.authorTong, Yunguangen
dc.date.accessioned2016-05-20T09:03:27Z-
dc.date.available2016-05-20T09:03:27Z-
dc.date.issued2015en
dc.identifier.citationZheng et al. BMC Medical Genomics (2015) 8:49 DOI 10.1186/s12920-015-0126-9en
dc.identifier.doi10.1186/s12920-015-0126-9en
dc.identifier.urihttp://hdl.handle.net/10150/610293-
dc.description.abstractBACKGROUND: Metastasis is the major cause of cancer-related death. Forkhead Box M1 (FoxM1) is a master regulator of tumor metastasis. This study aims to identify new FoxM1 targets in regulating tumor metastasis using bioinformatics tools as well as biological experiments. METHODS: Illumina microarray was used to profile WT and PTTG1 knockout HCT116 cells. R2 Genomics Analysis was used to identify PTTG1 as a potential FoxM1 targeted gene. Luciferase reporter array, EMSA and Chromatin Immunoprecipitation (ChIP) were used to determine the binding of FoxM1 to PTTG1 promoter. Boyden chamber assay was used to evaluate the effects of FoxM1-PTTG1 on cell migration and invasion. Splenic-injection induced liver metastasis model was used to evaluate the effects of FoxM1-PTTG1 on liver metastasis of colorectal cancer. RESULTS: Analyses of multiple microarray datasets derived from human colorectal cancer indicated that correlation levels of FoxM1 and pituitary tumor transforming gene (PTTG1) are highly concordant (R = 0.68 ~ 0.89, p = 2.1E-226 ~ 9.6E-86). FoxM1 over-expression increased and knock-down decreased PTTG1 expression. Luciferase reporter assay identified that the −600 to −300 bp region of PTTG1 promoter is important for FoxM1 to enhance PTTG1 promoter activity. EMSA and ChIP assays confirmed that FoxM1 directly binds to PTTG1 promoter at the −391 to −385 bp region in colorectal cancer cells. Boyden chamber assay indicated that both FoxM1 and PTTG1 regulate migration and invasion of HCT116 and SW620 colorectal cancer cells. Further in vivo assays indicated that PTTG1 knock out decreased the liver metastasis of FoxM1 over-expressing HCT116 cells. Microarray analyses identified 662 genes (FDR < 0.05) differentially expressed between WT and PTTG1−/− HCT116 cells. Among them, dickkopf homolog 1 (DKK1), a known WNT pathway inhibitor, was suppressed by PTTG1 and FoxM1. CONCLUSIONS: PTTG1 is a FoxM1 targeted gene. FoxM1 binds to PTTG1 promoter to enhance PTTG1 transcription, and FoxM1-PTTG1 pathway promotes colorectal cancer migration and invasion.en
dc.language.isoenen
dc.publisherBioMed Central Ltden
dc.relation.urlhttp://www.biomedcentral.com/1755-8794/8/49en
dc.rights© 2015 Zheng et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)en
dc.titleFoxM1 transactivates PTTG1 and promotes colorectal cancer cell migration and invasionen
dc.typeArticleen
dc.identifier.eissn1755-8794en
dc.contributor.departmentDepartment of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicineen
dc.contributor.departmentSun Yat-sen University Cancer Center ; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicineen
dc.contributor.departmentDepartment of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical Universityen
dc.contributor.departmentDivision of Epidemiology and Biostatistics, College of Public Health, University of Arizonaen
dc.contributor.departmentState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macauen
dc.contributor.departmentDepartment of Pathology, Xinxiang Medical Universityen
dc.contributor.departmentSchool of Pharmaceutical Science, Kunming Medical Universityen
dc.identifier.journalBMC Medical Genomicsen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.