👤 Jonna Alanko

Integrins are vital cell adhesion receptors with the ability to transmit extracellular matrix (ECM) cues to intracellular signalling pathways. ECM-integrin signalling regulates various cellular functions such as cell survival and movement. Integrin signalling has been considered to occur exclusively from adhesion sites at the plasma membrane (PM). However, recent data demonstrates integrin signalling also from endosomes. Integrin-mediated focal adhesion kinase (FAK) signalling is strongly dependent on integrin endocytosis, and endosomal FAK signalling facilitates cancer metastasis by supporting anchorage-independent growth and anoikis resistance. Here we discuss the possible mechanisms and functions of endosomal FAK signalling compared with its previously known roles in other cellular locations and discuss the potential of endosomal FAK as novel target for future cancer therapies. Show less

Integrin-containing focal adhesions transmit extracellular signals across the plasma membrane to modulate cell adhesion, signalling and survival. Although integrins are known to undergo continuous endo/exocytic traffic, the potential impact of endocytic traffic on integrin-induced signals is unknown. Here, we demonstrate that integrin signalling is not restricted to cell-ECM adhesions and identify an endosomal signalling platform that supports integrin signalling away from the plasma membrane. We show that active focal adhesion kinase (FAK), an established marker of integrin-ECM downstream signalling, localizes with active integrins on endosomes. Integrin endocytosis positively regulates adhesion-induced FAK activation, which is early endosome antigen-1 and small GTPase Rab21 dependent. FAK binds directly to purified endosomes and becomes activated on them, suggesting a role for endocytosis in enhancing distinct integrin downstream signalling events. Finally, endosomal integrin signalling contributes to cancer-related processes such as anoikis resistance, anchorage independence and metastasis. Show less