Cell adhesion and invasion mechanisms that guide developing axons

•Compare and contrast fibroblast focal adhesions with growth cone point contact adhesions.•Compare and contrast invadosomes of invasive cancer cells with analogous protrusions recently found on growth cones.•Discuss important future directions.

Axon extension, guidance and tissue invasion share many similarities to normal cell migration and cancer cell metastasis. Proper cell and growth cone migration requires tightly regulated adhesion complex assembly and detachment from the extracellular matrix (ECM). In addition, many cell types actively remodel the ECM using matrix metalloproteases (MMPs) to control tissue invasion and cell dispersal. Targeting and activating MMPs is a tightly regulated process, that when dysregulated, can lead to cancer cell metastasis. Interestingly, new evidence suggests that growth cones express similar cellular and molecular machinery as migrating cells to clutch retrograde actin flow on ECM proteins and target matrix degradation, which may be used to facilitate axon pathfinding through the basal lamina and across tissues.