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Bayarmagnai B, Perrin L, Pourfarhangi KE, Grana X, Tuzel E, Gligorijevic B
Invadopodia-mediated ECM degradation is enriched in the G1 phase of the cell cycle
J Cell Sci (2019) In process.
Tumor cell invasion and metastasis include assembly of invadopodia, protrusions capable of degrading the extracellular matrix (ECM). The effect of cell cycle progression on invadopodia has not been elucidated. In this study, using invadopodia- and cell cycle- fluorescent markers, we show in 2D and 3D cultures, as well as in vivo, that breast carcinoma cells assemble invadopodia and invade into the surrounding ECM preferentially during the G1 phase. The expression (MT1-MMP, cortactin) and localization (Tks5) of invadopodia components are elevated in G1 and cells synchronized in G1 phase exhibit significantly higher ECM degradation compared to the cells synchronized in S phase. The cyclin-dependent kinase inhibitor (CKI) p27(kip1) localizes to the sites of invadopodia assembly. Over-expression and stable knockdown of p27(kip1) show contrasting effects on invadopodia turnover and ECM degradation. Taken together, these findings suggest that expression of invadopodia components, as well as invadopodia function, are linked to cell cycle progression and that invadopodia is controlled by cell cycle regulators. Our results caution that this coordination between invasion and cell cycle must be considered when designing effective chemotherapies.
Publication Date: 2019-10-18.
PMCID: PMC6826011
Last updated on Friday, January 03, 2020