Breast and prostate cancer belong to the top four most common
cancers. Even though several effective therapy methods are available,
cancer still remains one of the leading causes of death all over the
world. PIM kinases have been reported to be upregulated in various
cancers, and to promote tumorigenesis there. Furthermore,
PIM kinases have become novel targets for anti-cancer drug
development, especially because of their specific structure,
which enables the design of selective inhibitors.



While the ability of PIM kinases to support cell survival
is well known, only recently have the effects on cell motility raised
interest. In addition, very little is known about the importance of PIM
kinases in cell metabolism, which is often altered in cancer cells.
This thesis focuses on studying the role of PIM kinases in prostate
cancer cell motility and breast cancer cell metabolism as well as breast
and prostate tumorigenesis.



PIM upregulation was shown to increase prostate cancer cell motility
and tumor progression, while a novel PIM inhibitor DHPCC-9 decreased
tumor size and the number of metastases in an orthotopic mouse model for
prostate cancer. Similar results were also gained after culturing
prostate cancer cells on a chicken embryo chorioallantoic membrane.
Thereafter the study concentrated more precisely on the PIM-dependent
signaling pathways. Interestingly, it was found that the
formation of prostate cancer metastases seems to depend on
PIM-mediated activation of the CXCR4/CXCL12 chemokine pathway as well as
the NOTCH1 receptor intracellular domain. In addition, PIM kinases
inactivate FOXP3 as well as GSK3B and support prostaglandin and
integrin-mediated cell motility in prostate cancer. In breast
cancer, cell energy metabolism depends on the interaction
of PIM kinases with the NOTCH1 intracellular domain. NOTCH1
activation by PIM also promotes hormone-dependent breast tumor growth in
the chorioallantoic membrane model.