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The molecular mechanism of the reversible switch between cell proliferation and migration. The regulatory function of the ERK pathway and ERK pathway scaffold RACK1

Objective

Recent studies suggest that the microenvironment surrounding primary tumor cells can temporarily change tumor cell gene expression, resulting in suppressed cell proliferation and increased cell motility. This genetic program allows tumor cells to invade the surrounding tissue, metastasize to distant parts of the body and suppress apoptosis induced by changes in the environment. Once cells reach a favorable milieu, they suppress migration, reactivate the proliferation program and expand in the target organ. Although many components involved in this switch between proliferative and migratory phenotypes have been identified, the precise molecular mechanism remains unknown. One of the protein shown to be specifically overexpresed in migratory but not in proliferating cells is adaptor/scaffold protein RACK1. We recently identified RACK1 as a scaffold-like protein in the ERK pathway which controls ERK activation and targets active ERK to specific intracellular compartments. My preliminary evidence indicates that the expression level of RACK1 correlates with the cell's ability to either migrate or proliferate. Thus, RACK1 may serve as a key molecular “switch” that controls whether ERK signaling regulates the proliferative or the migratory program. The goal of this research proposal is to understand how RACK1 and the ERK pathway regulate the switch between proliferative and migratory phenotypes and the contribution this “migratory switch” has on the development and progression of colorectal cancer.

Field of science

  • /social sciences/sociology/social problems/migration
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/cancer/colorectal cancer

Call for proposal

FP7-PEOPLE-IRG-2008
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

MIKROBIOLOGICKY USTAV AV CR V.V.I
Address
Videnska 1083
142 00 Praha 4
Czechia
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
Ondrej Schröffel (Dr.)