Open AccessInvadopodia-mediated ECM degradation is enriched in the G1 phase of the cell cycle
Author(s) -
Battuya Bayarmagnai,
Louisiane Perrin,
Kamyar Esmaeili Pourfarhangi,
Xavier Graña,
Erkan Tüzel,
Bojana Gligorijevic
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.227116
Subject(s) - invadopodia , microbiology and biotechnology , cortactin , podosome , extracellular matrix , biology , cell cycle , cell , cancer research , cancer cell , cytoskeleton , biochemistry , cancer , genetics
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) p27kip1 localizes to the sites of invadopodia assembly. Over-expression and stable knockdown of p27kip1 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.