The nuclear translocation of ERK1/2 as an anticancer target

Alexander Plotnikov, Karen Flores, Galia Maik-Rachline, Eldar Zehorai, Einat Kapri-Pardes, Denise A. Berti, Tamar Hanoch, Michal J. Besser and Rony Seger ()
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Alexander Plotnikov: The Weizmann Institute of Science
Karen Flores: The Weizmann Institute of Science
Galia Maik-Rachline: The Weizmann Institute of Science
Eldar Zehorai: The Weizmann Institute of Science
Einat Kapri-Pardes: The Weizmann Institute of Science
Denise A. Berti: The Weizmann Institute of Science
Tamar Hanoch: The Weizmann Institute of Science
Michal J. Besser: The Ella Lemelbaum Institute for Melanoma, The Sheba Medical Center, Ramat Gan, Tel Aviv University
Rony Seger: The Weizmann Institute of Science

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract A hallmark of the ERK1/2 functioning is their nuclear translocation, which is mainly required for the induction of proliferation. Activated ERK1/2 molecules that remain in the cytoplasm initiate other activities, including immediate feedback loops. Prevention of the nuclear translocation should therefore inhibit proliferation, without affecting cytoplasm-induced cellular processes. Here we present an NTS-derived myristoylated phosphomimetic peptide, which blocks the interaction of importin7 and ERK1/2, and consequently the nuclear translocation of the latter. In culture, the peptide induces apoptosis of melanoma cells inhibits the viability of other cancer cells, but has no effect on non-transformed, immortalized cells. It even inhibits the viability of PLX4032- and U0126-resistant melanoma cells. In xenograft models, the peptide inhibits several cancers, and acts much better than PLX4032 in preventing melanoma recurrence. This study provides a proof of concept for using the nuclear translocation of ERK1/2 as a drug target for the combat of various ERK1/2-related cancers.

Date: 2015
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DOI: 10.1038/ncomms7685

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