[Regulator proteins of actin dynamics as possible targets of antineoplastic therapies].

BACKGROUND

The ability of tumor cells to leave the primary tumor is prerequisite for metastatic spread. In previous studies, we identified regulator proteins of actin reorganization with essential functions in both synaptogenesis and tumor cell migration.

OBJECTIVE

The aim of the studies summarized in this article is to identify signaling pathways associated with actin-related proteins that might represent potential molecular targets for antiinvasive and/or antineoplastic therapies.

MATERIALS AND METHODS

We used immunohistochemical analyses of protein expression as well as in vitro techniques (cell culture, fluorescence microscopy, RNAi-based knockdown of protein expression, protein biochemistry and in vivo animal experiment substitutes).

RESULTS

We show that phosphorylation of Abelson interactor 1 (Abi1) is essential for the adhesion and invasion of colorectal carcinoma cells and might be targeted by the tyrosine kinase inhibitor STI571/Glivec®. HnRNP K, a protein interaction partner of Abi1, is upregulated in malignant melanoma in response to ionizing radiation; this upregulation is impaired upon application of the MEK inhibitor PD98059, enhancing radiosensivity of melanoma. Edelfosin, an alkyl-lipid blocker of the Abi1 interaction partner SK3, inhibits invasion of urothelial carcinoma cells.

CONCLUSION

The studies summarized in this overview confirm a central role for the investigated proteins in tumor cell invasion and resistance to antineoplastic therapies and identify possible molecular targets for novel therapeutic compounds.