The outgrowth of micrometastases is enabled by the formation of filopodium-like protrusions
Cette étude met en évidence un mécanisme par lequel la formation de protrusions cellulaires analogues à des filopodes favorise le processus métastatique
Disseminated cancer cells that have extravasated into the tissue parenchyma must interact productively with its extracellular matrix (ECM) components in order to survive, proliferate and form macroscopic metastases. The biochemical and cell-biological mechanisms enabling this interaction remain poorly understood. We find that the formation of elongated, integrin β1-containing adhesion plaques by cancer cells that have extravasated into the lung parenchyma enables the proliferation of these cells via activation of focal adhesion kinase (FAK). These plaques originate in and appear only after the formation of filopodium-like protrusions (FLPs) that harbor integrin β1 along their shafts. The cytoskeleton-regulating proteins Rif and mDia2 contribute critically to the formation of these protrusions and thereby enable the proliferation of extravasated cancer cells. Hence, the formation of FLPs represents a critical rate-limiting step for the subsequent development of macroscopic metastases.