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Published in: Journal of Neuro-Oncology 2/2010

01-04-2010 | Laboratory Investigation - Human/Animal Tissue

Identification of the role of Smad interacting protein 1 (SIP1) in glioma

Authors: Microgene Xia, Minghua Hu, Jun Wang, Yajun Xu, Xiaobing Chen, Yuedong Ma, Lei Su

Published in: Journal of Neuro-Oncology | Issue 2/2010

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Abstract

Glioma is an extremely aggressive and lethal form of brain cancer. Despite recent advances in diagnostics and treatments, prognosis for advanced patients suffering from these diseases remains poor. Therefore, identification of new therapeutic targets for glioma is of significant importance. In this study, we identified the important role of Smad interacting protein 1 (SIP1; also known as ZEB2) in glioma. We firstly found that SIP1 expression was high in four tumorigenic glioma cell lines but low in two nontumorigenic glioma cell lines. By knockdown or overexpression assay, we discovered that knockdown of SIP1 expression statistically significantly inhibited cell migration and invasion of tumorigenic glioma cells, while overexpression of SIP1 promoted cell migration and invasion of nontumorigenic glioma cells. SIP1 knockdown inhibits and overexpression promotes glioma cell clonogenicity in vitro. Further studies identified that SIP1 overexpression inhibits expression of E-cadherin and enhances expression of mesenchymal proteins such as fibronectin and vimentin. This study supports the rationale for developing SIP1 as a potential therapeutic and diagnostic target for gliomas.
Literature
1.
3.
go back to reference Sith Sathornsumetee JNR (2008) Designer therapies for glioblastoma multiforme. Ann N Y Acad Sci 1142:108–132CrossRefPubMed Sith Sathornsumetee JNR (2008) Designer therapies for glioblastoma multiforme. Ann N Y Acad Sci 1142:108–132CrossRefPubMed
6.
go back to reference Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Hofler H, Becker K (2002) Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer, ASIP, pp 1881–1891 Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Hofler H, Becker K (2002) Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer, ASIP, pp 1881–1891
7.
go back to reference Elloul S, Bukholt Elstrand M, Nesland J, Trope C, Kvalheim G, Goldberg I, Reich R, Davidson B (2005) Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer 103:1631–1643. doi:10.1002/cncr.20946 CrossRefPubMed Elloul S, Bukholt Elstrand M, Nesland J, Trope C, Kvalheim G, Goldberg I, Reich R, Davidson B (2005) Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer 103:1631–1643. doi:10.​1002/​cncr.​20946 CrossRefPubMed
10.
go back to reference Mikkers H, Allen J, Knipscheer P, Romeyn L, Hart A, Vink E, Berns A (2002) High-throughput retroviral tagging to identify components of specific signaling pathways in cancer. Nat Genet 32:153–159. doi:10.1038/ng950 CrossRefPubMed Mikkers H, Allen J, Knipscheer P, Romeyn L, Hart A, Vink E, Berns A (2002) High-throughput retroviral tagging to identify components of specific signaling pathways in cancer. Nat Genet 32:153–159. doi:10.​1038/​ng950 CrossRefPubMed
11.
go back to reference Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601. doi:10.1038/ncb1722 CrossRefPubMed Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601. doi:10.​1038/​ncb1722 CrossRefPubMed
12.
go back to reference Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, van Roy F (2001) The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 7:1267–1278. doi:10.1016/S1097-2765(01)00260-X CrossRefPubMed Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, van Roy F (2001) The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 7:1267–1278. doi:10.​1016/​S1097-2765(01)00260-X CrossRefPubMed
13.
go back to reference Bindels S, Mestdagt M, Vandewalle C, Jacobs N, Volders L, Noel A, Roy Fv, Berx G, Foidart JM, Gilles C (2006) Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene 25:4975–4985. doi:10.1038/sj.onc.1209511 CrossRefPubMed Bindels S, Mestdagt M, Vandewalle C, Jacobs N, Volders L, Noel A, Roy Fv, Berx G, Foidart JM, Gilles C (2006) Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene 25:4975–4985. doi:10.​1038/​sj.​onc.​1209511 CrossRefPubMed
14.
go back to reference Grunert S, Jechlinger M, Beug H (2003) Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol 4:657–665. doi:10.1038/nrm1175 CrossRefPubMed Grunert S, Jechlinger M, Beug H (2003) Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol 4:657–665. doi:10.​1038/​nrm1175 CrossRefPubMed
15.
16.
go back to reference Peña C, García JM, García V, Silva J, Domínquez R, Maximiano C, García de Herreros A, Muñoz A, Bonilla F (2006) The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas. Int J Cancer 119:2098–2104. doi:10.1002/ijc.22083 CrossRefPubMed Peña C, García JM, García V, Silva J, Domínquez R, Maximiano C, García de Herreros A, Muñoz A, Bonilla F (2006) The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas. Int J Cancer 119:2098–2104. doi:10.​1002/​ijc.​22083 CrossRefPubMed
17.
go back to reference Pena C, Garcia J, Silva J, Garcia V, Rodriguez R, Alonso I, Millan I, Salas C, de Herreros A, Munoz A (2005) E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations. Hum Mol Genet 14:3361. doi:10.1093/hmg/ddi366 CrossRefPubMed Pena C, Garcia J, Silva J, Garcia V, Rodriguez R, Alonso I, Millan I, Salas C, de Herreros A, Munoz A (2005) E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations. Hum Mol Genet 14:3361. doi:10.​1093/​hmg/​ddi366 CrossRefPubMed
18.
go back to reference Spoelstra N, Manning N, Higashi Y, Darling D, Singh M, Shroyer K, Broaddus R, Horwitz K, Richer J (2006) The transcription factor ZEB1 is aberrantly expressed in aggressive uterine cancers, AACR, pp 3893–3902 Spoelstra N, Manning N, Higashi Y, Darling D, Singh M, Shroyer K, Broaddus R, Horwitz K, Richer J (2006) The transcription factor ZEB1 is aberrantly expressed in aggressive uterine cancers, AACR, pp 3893–3902
22.
Metadata
Title
Identification of the role of Smad interacting protein 1 (SIP1) in glioma
Authors
Microgene Xia
Minghua Hu
Jun Wang
Yajun Xu
Xiaobing Chen
Yuedong Ma
Lei Su
Publication date
01-04-2010
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2010
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-009-0015-1

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