Figure 6.

Proposed role of TNK2 in invasion and metastasis. (a) We propose that the effects of TNK2 on cell migration and the cytoskeleton are mediated by epidermal growth factor receptor (EGFR). The effects may also be mediated by breast cancer antioestrogen resistance 1 (BCAR1) downstream of TNK2, but this signal is independent from that which leads to TNK2-induced EGFR cell surface stabilisation. Previous work showed Cdc42 functions in a positive feedback loop to maintain EGFR on the cell surface, and we suggest that TNK2 functions as part of this loop. Experiments with the EGFR inhibitor PD153035 demonstrated that reduced migratory capacity results from EGFR inhibition, and that siRNA directed against TNK2 similarly inhibits migration and invasion by reduction of the number of cell surface receptors available for activation. (b) BCAR1 silencing, in contrast, inhibits migration and invasion downstream of Cdc42/TNK2 but does not contribute to the positive feedback effect on the EGFR.