The actin cytoskeleton plays a critical role in
cancer cell invasion and
metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate
cancer cell invasion by focusing the secretion of extracellular matrix-degrading
enzymes, including
matrix metalloproteinases (
MMPs). In this study, we investigated the nuclear role of
cysteine-rich
protein 2 (CRP2), a two LIM domain-containing
F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in
breast cancer cells. We found that
F-actin depolymerization stimulates the translocation of CRP2 into the nucleus, resulting in an increase in the transcript levels of pro-invasive and pro-metastatic genes, including several members of the
MMP gene family. We demonstrate that in the nucleus, CRP2 interacts with the
transcription factor serum response factor (SRF), which is crucial for the expression of MMP-9 and MMP-13. Our data suggest that CRP2 and SRF cooperate to modulate of
MMP expression levels. Furthermore, Kaplan-Meier analysis revealed a significant association between high-level expression of SRF and shorter overall survival and distant
metastasis-free survival in
breast cancer patients with a high CRP2 expression profile. Our findings suggest a model in which CRP2 mediates the coordination of cytoplasmic and nuclear processes driven by actin dynamics, ultimately resulting in the induction of invasive and metastatic behavior in
breast cancer cells.