Research - Centre for Biotechnology

Research > Research areas > Cancer Cell Signaling

Cancer Cell Signaling

Group leader

Jukka Westermarck, Research Professor of the Finnish Cancer Institute
Turku Centre for Biotechnology
jukka.westermarck [at] utu.fi

Contact information

Turku Centre for Biotechnology
P.O. Box 123, BioCity
(Street addr. Tykistökatu 6 B)
FIN-20521 Turku, Finland
+358-2-3338621 (Jukka Westermarck)
+358-2-333-8696 (Group members)

Description of the Project

The goal of our research group is to identify novel signalling mechanisms involved in malignant cell growth by isolating protein complexes associated with proteins previously demonstrated to have an important role in cancer progression. To identify protein complexes, we use tandem affinity purification (TAP) and Strep-tag purification methods, both proven to be suitable for purification of signalling protein complexes from mammalian cells in culture. Identification of novel proteins involved in malignant growth may also reveal novel possibilities for intervention in the therapy of cancer and other hyperproliferative diseases.

Based on our recent work, we have identified several novel interacting proteins for signalling proteins such as AP-1 transcription factor c-Jun, MAPK kinase MEK1, and protein phosphatase PP2A. Most of our future work will be focused on characterization of PP2A interaction partner CIP2A, that we have demonstrated to inhibit PP2A in human malignancies. As PP2A inhibition has been recognized as a prerequisite for human cell transformation, it is plausible that further understanding of the function of CIP2A will reveal fundamental novel information about the basic mechanisms of cancer progression. The overall goal of the proposed project is to study the function and importance of CIP2A in cancer progression by using combination of molecular biology, cell biology and functional genetics methods. As our current results suggest that targeting CIP2A could be beneficial in the treatment of cancer, our goal is also to develop research models for evaluating the suitability of CIP2A as a novel drug target for cancer therapies. In addition, our aim is to purify new protein complexes related to regulation of PP2A activity in cancer cells.

Group members

Coordinator

Tiina Arsiola, Ph.D.

Post-doctoral Fellows

Anna Cvrljevic, Ph.D.
Juha Okkeri, Ph.D.

Graduate students

Anni Laine, M.Sc.
Amanpreet Kaur, M.Sc
Otto Kauko, M.Sc., B.M.
Xi Qiao, M.Sc.
Eleonora Sittig, B.Sc.

Technical Personnel

Taina Kalevo-Mattila
Inga Pukonen

Funding

The Academy of Finland, University of Turku Graduate School/Turku Graduate School of Biomedical Sciences, Sigrid Juselius Foundation, Cancer Research Foundation of Finland.

Selected Publications

Laine A, Sihto H, Come C, Rosenfeldt MT, Zwolinska A, Niemelä M, Khanna A, Chan EK, Kähäri VM, Kellokumpu-Lehtinen PL, Sansom OJ, Evan GI, Junttila MR, Ryan KM, Marine JC, Joensuu H, Westermarck J. Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1. Cancer Discov. 2013 Jan 10;3(2):182-97

Ventelä S, Mäkelä J-A, Kulmala J, Westermarck J, and Toppari J: Identification and regulation of a stage-specific stem cell niche enriched by Nanog positive spermatogonial stem cells in the mouse testis. STEM CELLS,2012 May;30(5):1008-20.

Ventelä, S., Come, C., Mäkelä, J.-A., Hobbs, R.M., Mannermaa, L., Kallajoki, M., Chan, E.K., Pandolfi, P.P., Toppari, J. and Westermarck, J: CIP2A promotes proliferation of spermatogonial progenitor cells and spermatogenesis in mice. Plos ONE, 2012;7(3).

Niemelä M, Kauko O, Sihto H, Mpindi J-P, Nicorici D, Pernilä P, Kallioniemi O-P, Joensuu H, Hautaniemi S, and Westermarck J: CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes. Oncogene, 2012; Sep 27;31(39):4266-78.

Khanna A, Okkeri J, Bilgen T, Tiirikka T, Vihinen V, Visakorpi T, and Westermarck J; ETS1 mediates MEK1/2-dependent overexpression of Cancerous inhibitor of protein phosphatase 2A (CIP2A) in human cancer cells. PLoS ONE, 6(3): e17979, 2011.

Come C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X, Jonkers J, Ivaska J, Isola J, Darbon J-M, Kallioniemi O-P, and Thezenas S and Westermarck J; CIP2A is associated with human breast cancer aggressivity. Clinical Cancer Research, 15, 5092-5100, 2009.

Khanna A, Böckelman C, Hemmes A, Junttila MR, Wiksten J-P, Lundin P, Junnila S, Murphy D, Evan GI, Haglund C, Westermarck J*, and Ristimäki A*; c-Myc-dependent regulation and prognostic role of CIP2A in gastric cancer. Journal of the National Cancer Institute, 101, 793-805, 2009. *equal contribution

Puustinen P, Junttila MR, Vanhatupa S, Sablina AA, Hector ME, Teittinen K, Raheem O, Ketola K, Lin S, Kast J, Haapasalo H, Hahn WC, and Westermarck J; PME-1 Protects ERK Pathway activity from Protein Phosphatase 2A-mediated Inactivation in human malignant glioma. Cancer Research, 69, 2870-2877, 2009.

Wu J, Ovaska K, Vallenius T, Westermarck J, Mäkelä TP, and Hautaniemi S; Protein-protein interaction portal for network level analysis. Nature Methods, 6, 75-77, 2009

Junttila, MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, Ala-aho R, Nielsen C, Ivaska J, Taya Y, Lu SL, Li S, Chan EKL, Wang X-J, Grenman R, Kast J, Kallunki T, Sears R, Kähäri V-M, Westermarck J; CIP2A Inhibits PP2A in Human Malignancies. Cell, 130, 51–62, 2007.

Reviews

Westermarck J; Regulation of transcription factor function by targeted protein degradation: an overview focusing on p53, c-Myc, and c-Jun. Methods Mol Biol., 647, 31-36, 2010.

Westermarck J, Hahn WC; Multiple pathways regulated by the tumor suppressor PP2A in transformation. Trends in Molecular Medicine, 14,152-160, 2008.

Junttila MR, Li S-P, Westermarck J; Phosphatase-mediated cross-talk between MAPK signaling pathways in the regulation of cell survival. The FASEB Journal, 22, 954-965, 2008.