Cell migration requires cells to sense and interpret an array of extracellular signals to precisely co-ordinate adhesion dynamics, local application of mechanical force, polarity signalling and cytoskeletal dynamics. Adhesion receptors and growth factor receptors (GFRs) exhibit functional and signalling characteristics that individually contribute to cell migration. Integrins transmit bidirectional mechanical forces and transduce long-range intracellular signals. GFRs are fast acting and highly sensitive signalling machines that initiate signalling cascades to co-ordinate global cellular processes. Syndecans are microenvironment sensors that regulate GTPases to control receptor trafficking, cytoskeletal remodelling and adhesion dynamics. However, an array of crosstalk mechanisms exists, which co-ordinate and integrate the functions of the different receptor families. Here we discuss the nature of adhesion receptor and GFR crosstalk mechanisms. The unifying theme is that efficient cell migration requires precise spatial and temporal co-ordination of receptor crosstalk. However, a higher order of complexity emerges; whereby multiple crosstalk mechanisms are integrated and subject to both positive and negative feedbacks. Exquisite and sensitive control of these mechanisms ensures that mechanical forces and pro-migratory signals are triggered in the right place and at the right time during cell migration. Finally, we discuss the challenges, and potential therapeutic benefits, associated with deciphering this complexity.

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