Receptor Tyrosine Kinases in Cancer and Development
Principal investigator:
Klaus Elenius
Professor
Contact Information
Office Medisiina Building C4, room C456
Address
Medical Biochemistry and Genetics
Institute of Biomedicine
Kiinamyllynkatu 10
20520 TURKU, FINLAND
Phone +358-2-333 7240
Fax +358-2-230-1280
Email klaele (at) utu.fi
Description of the project
Our goal is to understand how receptor tyrosine kinases (RTK) regulate the pathogenesis of human diseases, such as cancer. This information is needed for the development of molecularly targeted therapies. To recognize aberrations of RTK signaling in diseased tissue our laboratory also works on the molecular mechanism by which RTKs control normal processes, such as embryonic development. The work mainly focuses on the ErbB family of RTKs. Our laboratory has contributed to the field by e.g. by characterizing novel RTK signaling mechanisms, by identifying novel ErbB4 isoforms, and by determining the role of ErbBs and their ligands in angiogenesis.
Current topics
Novel receptor tyrosine kinase signaling mechanisms
ErbB receptor signaling in angiogenesis
Biological role of novel ErbB4 isoforms in diseases and development
Analysis of ErbB4 isoforms as drug targets
Prognostic and predictive significance of ErbB receptors
Receptor tyrosine kinases in pediatric malignancies
Development of preclinical models for testing receptor tyrosine kinase inhibitors
Lab members
PhD Theses
Ville Veikkolainen 2011 Regulation of cell growth, death, and polarization by ERBB4
Maija Holmen 2010 Role of ErbB2 and ErbB4 in cancer growth, prognosis and as targets for immunotherapy
Erika Iivanainen 2008 ErbB ligands in angiogenesis
Maria Sundvall 2007 Signaling of ErbB4 isoforms in cancer
Marjut Borgenström 2006 Sulfated polysaccharides in the regulation of fibroblast growth factor signaling, cancer
cell proliferation, and metastasis
Teemu Junttila 2005 Signaling mechanisms and prognostic significance of ErbB4 isoforms in cancer
Publications
2011
Veikkolainen, V.; Vaparanta, K.; Halkilahti, K.; Iljin, K.; Sundvall, M. & Elenius, K. 2011: Function of ERBB4 is determined by alternative splicing. - Cell Cycle 10-16:1-11.
Veikkolainen, V.; Naillat*, F.; Railo*, A.; Chi*, L.; Manninen*, A.; Hohenstein*, P.; Hastie*, N.; Vainio*, S. & Elenius, K. 2011: ErbB4 modulates tubular cell polarity and lumen diameter during kidney development. - J Am Soc Nephorol 23:1?11.
2010
Hollmén, M. & Elenius, K. 2009: Potential of ErbB4 antibodies for cancer therapy. - Future Oncol 6:37-53.
Iivanainen, E. & Elenius, K. 2010: ErbB targeted and angiogenesis. - Curr Vasc Pharmacol 1:421-31.
Jokilehto, T., Högel, H., Heikkinen, P., Rantanen, K., Elenius, K., Sundström, J. & Jaakkola, P.M. 2010: Retention of prolyl hydroxylase PHD2 in the cytoplasm prevents PHD2-induced anchorage-independent carcinoma cell growth. - Exp Cell Res 15:1169-1178.
Sundvall, M., Karrila, A., Nordberg, J., Grenman, R. & Elenius, K. 2010: EGFR tarketing drugs in the treatment of head and neck squamous cell carcinoma. - Expert Opin Emerg Drugs, Apr 23 15:1-17.
Sundvall, M., Veikkolainen, V., Kurppa, K., *Salah, Z., Tvorogov, D., *Joop van Zoelen, E. *Aqeilan, R. & Elenius, K. 2010: Cell death or survival promoted by alternative isoforms of ErbB4. - Mol Biol Cell 21: 1-12.
2009
Hollmén, M., Määttä, J.A., *Bald, L., *Sliwkowski, M.X. & Elenius, K. 2009: Suppression of breast cancer cell growth by a monoclonal antibody targeting cleavable ErbB4 isoforms. - Oncogene 28:1309-1319.
Iivanainen, E., *Lauttia, S., Zhang, N., Tvorogov, D., Kulmala, J., Grenman, R., *Salven, P. & Elenius, K. 2009: The EGFR inhibitor gefitinib suppresses recruitment of pericytes and bone marrow-derived perivascular cells into tumor vessels. - Microvasc Res
Kurppa, K. & Elenius, K. 2009: Mutated ERBB4: a novel drug target in metastatic melanoma? - Pigment Cell Melanoma Res 1-2.
*Muraoka-Cook, R.S., *Sandahl, M.A., *Strunk, K.E., *Miraglia, L.C., *Husted, C., *Hunter, D.M., Elenius, K., *Chodosh, L.A. and *Earp, H.S. 2009: ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert opposing effects on the mammary epithelium in vitro. -Mol Cell Biol 29:4935?4948.
Määttä, J.A., Olli, K., Henttinen, T., Tuittila, M.T., Elenius, K. & Salmivirta, M. 2009: Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor. - BMC Cell Biol 10:5.
Zhang, N., Erjala, K., Kulmala, J., *Qiu, X., Sundvall, M., Elenius, K. & Grenman, R. 2009: Concurrent cetuximab, cisplatin and radiation for squamous cell carcinoma of the head and neck in vitro. - Radiother Oncol
Zhang, N., Erjala, K., Kulmala, J., *Qiu, X., Sundvall, M., Elenius, K. & Grenman, R. 2009: Concurrent cetuximab, cisplatin and radiation for squamous cell carcinoma of the head and neck in vitro. - Radiother Oncol
2008
Paatero, I. & Elenius, K. 2008: ErbB4 and its isoforms: Patentable drug targets -Recent Patents on DNA & Gene Sequences 2:27?33.
Sundvall, M., Iljin, K., *Kilpinen, S., Sara, H., *Kallioniemi, O-P. & Elenius, K. 2008: Role of ErbB4 in breast cancer. - J Mammary Gland Biol Neoplasia
Sundvall, M., Korhonen, A., Paatero, I., *Gaudio, E., *Melino, G., *Croce, C.M., *Aqeilan, R.I. & Elenius, K. 2008: Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms. - Proc Natl Acad Sci USA 105:4162?4167.
2007
*Aqeilan, R., *Donati, V., *Gaudio, E., *Nicoloso, M., Sundvall, M., Korhonen, A., *Lundin, J., *Isola, J., *Sudol, M., *Joensuu, H., *Croce, C. & Elenius, K. 2007: Association of Wwox with ErbB4 in breast cancer. - Cancer Res 67:9330-9336.
Borgenström, M., Wärri, A., Hiilesvuo, M., Käkönen, R., *Käkönen, S., *Nissinen, L., *Pihlavisto, M., *Marjamäki, A., *Vlodavsky, I., *Naggi, A., *Torri, G., *Casi, B., Veromaa, T., Salmivirta, M. & Elenius, K. 2007: O-sulfated bacterial polysaccharides with low anticoagulant activity inhibit metastasis. - Semin Thromb Hemost 33:547-556.
Erjala, K., Zhang, N., Sundvall, M., Kulmala, J., Elenius, K. & Grenman, R. 2007: Concomitant chemoirradiation with vinorelbine and gefitinib induced additive effect in head and neck squamous cell carcinoma cell line in vitro. - Radiother Oncol 85:138-145.
Iivanainen, E., Paatero, I., Heikkinen, S-M., Junttila, T., *Cao, R., *Klint, P., Jaakkola, P., *Cao, Y. & Elenius, K. 2007: Intra- and extracellular signaling by endothelial neuregulin-1. - Exp Cell Res 313:2896-2909.
2006
Elenius, K. 2006: Epidermaalisen kasvutekijän reseptorin estäjät syövän hoidossa. - Duodecim 122:1331-1338.
Erjala, K., Sundvall, M., Junttila, T.T., Zhang, N., Savisalo, M., Mali, P., Kulmala, J., Pulkkinen, J., Grenman, R. & Elenius, K. 2006: Signaling via ErbB2 and ErbB3 associates with resistance and Epidermal Growth Factor Receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells. - Clin Cancer Res 12:4103-4111.
*Järvellä, S., *Helin, H., *Haapasalo, J., *Järvellä, T., Junttila, T.T., Elenius, K., *Tanner, M., *Haapasalo, H. & *Isola, J. 2006: Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization: association with clinicopathological features and patient survival. - Neuropath Appl Neuro 32:441-450.
Määttä, J.A., Sundvall, M., Junttila, T.T., Peri, L., Laine, V.J.O., *Isola, J., *Egeblad, M. & Elenius, K. 2006: Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4 isoform promote ligand-independent survival and cancer cell growth. - Mol Biol Cell 17:67-79.