Group Leader

Jukka Westermarck
Research Director and Professor of Cancer Biology,
Turku Bioscience
jukka.westermarck [at] utu.fi
Follow @westermarcklab https://orcid.org/0000-0001-7478-3018

Contact Information

Turku Bioscience P.O. Box 123, BioCity
(Street addr. Tykistökatu 6 B)
FIN-20521 Turku, Finland
+358-294502880 (Jukka Westermarck)
+358-294503790 (Group members)

Description of the Research

Most characteristics of malignant cell growth are driven by phosphorylation-dependent signaling pathways that are deregulated in cancer cells. Whereas the regulation and function of many oncogenic kinases are well understood, the roles of protein phosphatases in cancer initiation, progression and therapy resistance are yet poorly understood.

The focus of our laboratory is to understand the role and regulation of PP2A and other phosphatases in human cancers, and especially function of PP2A inhibitor proteins as human oncoproteins. To achieve this, we use a combination of advanced cell and molecular biology approaches combined with genetically modified mouse cancer models. We also have special interest on targeted therapies against PP2A inhibitor proteins. Our laboratory identified CIP2A as a novel PP2A inhibitor protein in human malignancies (Cell, 2007), and was the first to demonstrate cancer-promoting roles for both CIP2A and another PP2A inhibitor protein PME-1 (Cancer Research, 2009). Expression of both of these proteins shows a strong association with tumor progression in human patients (Cancer Discovery 2013, Cancer Res. 2021) and their high expression is linked to cancer drug resistance (Cancer Res. 2016, Sci.Transl. Med, 2018). Based both on these results, and on wide-spectrum role of PP2A on cellular signaling, we hypothesize that re-activation of PP2A, via targeting of its endogenous inhibitory proteins such as CIP2A, could be used as a general strategy for multi-target inhibition of chemoresistance in common human cancer types (Sci. Transl. Med. 2021). Our laboratory continues exploring structural determinants of CIP2A to facilitate its targeting (Nat. Comm 2023). On the other hand, inhibition of oncogneic phoshatases, such as DUSP6, appears also a potent novel cancer therapy approach (Embo Mol. Med., 2024).

Funding