Cell cycle dependence of invadopodia

Invadopodia are membrane protrusions that are responsible for extracellular matrix (ECM) degradation, and facilitate cancer invasion and metastasis. Although it had been shown that the extrinsic microenvironment controls invadopodia assembly, only a small percentage of cancer cells in a given microenvironment typically present invadopodia, raising the question of whether cell-intrinsic factors, such as the cell cycle, are also involved in their assembly. In their study (Bayarmagnai et al., 2019), Bojana Gligorijevic and co-workers address this question by simultaneously visualising cell cycle progression and invadopodia assembly in 2D and 3D spheroid cultures of breast carcinoma cells, as well as in vivo. They observe that cells degrade and invade ECM during the G1 phase of the cell cycle. This is mediated by an increase in the expression levels of key invadopodia components. Interestingly, depletion of Tks5, which abolishes invadopodia formation, altered cell cycle progression with an increase in the duration of S phase. Finally, the authors show that the cyclin-dependent kinase inhibitor p27^kip1 is recruited to sites of invadopodia assembly and regulates their function and dynamics. Taken together, this work clearly suggests that invadopodia function is linked to the cell cycle. This could be important in the context of chemotherapeutics that arrest cancer cells in G1, as they may, in fact, promote invasive and metastatic behaviour.