Skip to main content
Top
Published in: Clinical & Experimental Metastasis 2/2009

01-02-2009 | Research Paper

Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo

Authors: Sumanta Goswami, Ulrike Philippar, Daqian Sun, Antonia Patsialou, Jacob Avraham, Weigang Wang, Francesca Di Modugno, Paola Nistico, Frank B. Gertler, John S. Condeelis

Published in: Clinical & Experimental Metastasis | Issue 2/2009

Login to get access

Abstract

We have studied the gene expression pattern of invasive primary mammary tumor cells using a unique in vivo invasion assay that isolates the invasive tumor cells by chemotaxis. One of the genes upregulated in the invasive tumor cells is Mena, an actin binding protein involved in the regulation of cell motility. There are multiple known splice variants of Mena accounted for by four alternatively included exons, +, ++, +++ and 11a. Using the in vivo invasion assay in rats and mice with mammary tumors we observed that two isoforms of Mena, ++ and +++, are upregulated in the invasive tumor cells and one isoform, 11a, is downregulated. The Mena isoform switching pattern described here may provide a new biomarker for the presence of metastatic cancer cells and for prognosis.
Appendix
Available only for authorised users
Literature
10.
go back to reference Philippar U, Roussos ET, Oser M, Yamaguchi H, Kim H, Giampieri S, Wang Y, Goswami S, Wyckoff JB, Sahai E, Condeelis JS, Gertler FB (2008) A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev Cell (in press) Philippar U, Roussos ET, Oser M, Yamaguchi H, Kim H, Giampieri S, Wang Y, Goswami S, Wyckoff JB, Sahai E, Condeelis JS, Gertler FB (2008) A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev Cell (in press)
15.
go back to reference Loureiro JJ, Rubinson DA, Bear JE et al (2002) Critical roles of phosphorylation and actin binding motifs, but not the central proline-rich region, for Ena/vasodilator-stimulated phosphoprotein (VASP) function during cell migration. Mol Biol Cell 13(7):2533–2546. doi:10.1091/mbc.E01-10-0102 PubMedCrossRef Loureiro JJ, Rubinson DA, Bear JE et al (2002) Critical roles of phosphorylation and actin binding motifs, but not the central proline-rich region, for Ena/vasodilator-stimulated phosphoprotein (VASP) function during cell migration. Mol Biol Cell 13(7):2533–2546. doi:10.​1091/​mbc.​E01-10-0102 PubMedCrossRef
16.
go back to reference Di Modugno F, Bronzi G, Scanlan MJ et al (2004) Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8 + T-cell immune response. Int J Cancer 109(6):909–918. doi:10.1002/ijc.20094 PubMedCrossRef Di Modugno F, Bronzi G, Scanlan MJ et al (2004) Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8 + T-cell immune response. Int J Cancer 109(6):909–918. doi:10.​1002/​ijc.​20094 PubMedCrossRef
17.
go back to reference Di Modugno F, DeMonte L, Balsamo M et al (2007) Molecular cloning of hMena (ENAH) and its splice-variant hMena + 11a. Epidermal growth factor (EGF) increases their expression and stimulates hMena + 11a phosphorylation in breast cancer cell lines. Cancer Res 67:2657–2665. doi:10.1158/0008-5472.CAN-06-1997 PubMedCrossRef Di Modugno F, DeMonte L, Balsamo M et al (2007) Molecular cloning of hMena (ENAH) and its splice-variant hMena + 11a. Epidermal growth factor (EGF) increases their expression and stimulates hMena + 11a phosphorylation in breast cancer cell lines. Cancer Res 67:2657–2665. doi:10.​1158/​0008-5472.​CAN-06-1997 PubMedCrossRef
18.
go back to reference Di Modugno F, Mottolese M, Di Benedetto A et al (2006) The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors. Clin Cancer Res 12(5):1470–1478. doi:10.1158/1078-0432.CCR-05-2027 PubMedCrossRef Di Modugno F, Mottolese M, Di Benedetto A et al (2006) The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors. Clin Cancer Res 12(5):1470–1478. doi:10.​1158/​1078-0432.​CCR-05-2027 PubMedCrossRef
19.
go back to reference Urbanelli L, Massini C, Emiliani C et al (2006) Characterization of human Enah gene. Biochim Biophys Acta 1759(1–2):99–107PubMed Urbanelli L, Massini C, Emiliani C et al (2006) Characterization of human Enah gene. Biochim Biophys Acta 1759(1–2):99–107PubMed
22.
go back to reference Wyckoff J, Segall J, Condeelis J (2000) The collection of the motile population of cells from a living tumor. Cancer Res 60:5401–5404PubMed Wyckoff J, Segall J, Condeelis J (2000) The collection of the motile population of cells from a living tumor. Cancer Res 60:5401–5404PubMed
23.
go back to reference Wyckoff J, Segall JE, Condeelis J (2005) Single-cell imaging in animal tumors in vivo. In: Spector D, Goldman R (eds) Live cell imaging, a laboratory manual, chap 22. Cold Spring Harbor Laboratory Press, pp 409–422 Wyckoff J, Segall JE, Condeelis J (2005) Single-cell imaging in animal tumors in vivo. In: Spector D, Goldman R (eds) Live cell imaging, a laboratory manual, chap 22. Cold Spring Harbor Laboratory Press, pp 409–422
24.
go back to reference Pino MS, Balsamo M, Di Modugno F et al (2008) Human Mena + 11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clin Cancer Res 14(15):4943–4950. doi:10.1158/1078-0432.CCR-08-0436 PubMedCrossRef Pino MS, Balsamo M, Di Modugno F et al (2008) Human Mena + 11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clin Cancer Res 14(15):4943–4950. doi:10.​1158/​1078-0432.​CCR-08-0436 PubMedCrossRef
Metadata
Title
Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo
Authors
Sumanta Goswami
Ulrike Philippar
Daqian Sun
Antonia Patsialou
Jacob Avraham
Weigang Wang
Francesca Di Modugno
Paola Nistico
Frank B. Gertler
John S. Condeelis
Publication date
01-02-2009
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 2/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-008-9225-8

Other articles of this Issue 2/2009

Clinical & Experimental Metastasis 2/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine