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Erschienen in: Clinical and Translational Oncology 5/2016

14.09.2015 | Research Article

Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer

verfasst von: H. G. Zhang, X. W. Xu, X. P. Shi, B. W. Han, Z. H. Li, W. H. Ren, P. J. Chen, Y. F. Lou, B. Li, X. Y. Luo

Erschienen in: Clinical and Translational Oncology | Ausgabe 5/2016

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Abstract

Background

The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis.

Methods

We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC.

Results

The results showed that high expression of FOXM1 staining was 85.44 % (88/103) in 103 cases of CRC and 20.39 % (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines.

Conclusions

Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.
Literatur
1.
Zurück zum Zitat Perencevich M, Stoffel EM. A multidisciplinary approach to the diagnosis and management of multiple colorectal polyps. Gastroenterol Hepatol. 2011;7:420. Perencevich M, Stoffel EM. A multidisciplinary approach to the diagnosis and management of multiple colorectal polyps. Gastroenterol Hepatol. 2011;7:420.
3.
Zurück zum Zitat Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844–57.CrossRefPubMed Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844–57.CrossRefPubMed
4.
Zurück zum Zitat Koo CY, Muir KW, Lam EW. FOXM1: from cancer initiation to progression and treatment. Biochim Biophys Acta. 2012;1819:28–37.CrossRef Koo CY, Muir KW, Lam EW. FOXM1: from cancer initiation to progression and treatment. Biochim Biophys Acta. 2012;1819:28–37.CrossRef
5.
Zurück zum Zitat Katoh M. Human FOX gene family (review). Int J Oncol. 2004;5:1495–500. Katoh M. Human FOX gene family (review). Int J Oncol. 2004;5:1495–500.
6.
Zurück zum Zitat Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 2002;62:4773–80.PubMed Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 2002;62:4773–80.PubMed
7.
Zurück zum Zitat Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 2006;66:1712–20.CrossRefPubMedPubMedCentral Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 2006;66:1712–20.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 2006;66:3593–602.CrossRefPubMed Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 2006;66:3593–602.CrossRefPubMed
9.
Zurück zum Zitat Li Q, Zhang N, Jia Z, Le X, Dai B, Wei D, et al. Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res. 2009;69:3501–9.CrossRefPubMedPubMedCentral Li Q, Zhang N, Jia Z, Le X, Dai B, Wei D, et al. Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res. 2009;69:3501–9.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Madureira PA, Varshochi R, Constantinidou D, Francis RE, Coombes RC, Yao KM, et al. The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells. J Biol Chem. 2006;281:25167–76.CrossRefPubMed Madureira PA, Varshochi R, Constantinidou D, Francis RE, Coombes RC, Yao KM, et al. The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells. J Biol Chem. 2006;281:25167–76.CrossRefPubMed
11.
Zurück zum Zitat Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, et al. The forkhead box M1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 2006;66:2153–61.CrossRefPubMed Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, et al. The forkhead box M1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 2006;66:2153–61.CrossRefPubMed
12.
Zurück zum Zitat Jiang LZ, Wang P, Deng B, Huang C, Tang WX, Lu HY, et al. Overexpression of forkhead box M1 transcription factor and nuclear factor-κB in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis. Hum Pathol. 2011;42:1185–93.CrossRefPubMed Jiang LZ, Wang P, Deng B, Huang C, Tang WX, Lu HY, et al. Overexpression of forkhead box M1 transcription factor and nuclear factor-κB in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis. Hum Pathol. 2011;42:1185–93.CrossRefPubMed
13.
Zurück zum Zitat Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217:998–1003.CrossRefPubMed Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217:998–1003.CrossRefPubMed
14.
Zurück zum Zitat Liotta LA, Steeq PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–36.CrossRefPubMed Liotta LA, Steeq PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–36.CrossRefPubMed
15.
Zurück zum Zitat Chandran UR, Ma C, Dhir R, Bisceglia M, Lyons-Weiler M, Liang W, et al. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer. 2007;7:64–85.CrossRefPubMedPubMedCentral Chandran UR, Ma C, Dhir R, Bisceglia M, Lyons-Weiler M, Liang W, et al. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer. 2007;7:64–85.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Park HJ, Gusarova G, Wang Z, Carr JR, Li J, Kim KH, et al. Deregulation of FoxM1b leads to tumour metastasis. EMBO Mol Med. 2011;1:21–34.CrossRef Park HJ, Gusarova G, Wang Z, Carr JR, Li J, Kim KH, et al. Deregulation of FoxM1b leads to tumour metastasis. EMBO Mol Med. 2011;1:21–34.CrossRef
17.
Zurück zum Zitat Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161:1163–77.CrossRefPubMedPubMedCentral Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161:1163–77.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF, Detmar M. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med. 2005;201:1089–99.CrossRefPubMedPubMedCentral Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF, Detmar M. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med. 2005;201:1089–99.CrossRefPubMedPubMedCentral
Metadaten
Titel
Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer
verfasst von
H. G. Zhang
X. W. Xu
X. P. Shi
B. W. Han
Z. H. Li
W. H. Ren
P. J. Chen
Y. F. Lou
B. Li
X. Y. Luo
Publikationsdatum
14.09.2015
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 5/2016
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1400-1

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