Intravital imaging of Wnt/?-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis

Wnt signalling has been implicated as a driver of tumour cell metastasis, but less is known about which branches of Wnt signalling are involved and when they act in the metastatic cascade. Here, using a unique intravital imaging platform and fluorescent reporters, we visualised D-catenin/TCF-dependent and ATF2-dependent signalling activities during human cancer cell invasion, intravasation and metastatic lesion formation in the chick embryo host. We found that cancer cells readily shifted between states of low and high canonical Wnt activity. Cancer cells that displayed low Wnt canonical activity showed higher invasion and intravasation potential in primary tumours and in metastatic lesions. In contrast, cancer cells showing low ATF2-dependent activity were significantly less invasive both at the front of primary tumours and in metastatic lesions. Simultaneous visualisation of both these reporters using a double-reporter cell line confirmed their complementary activities in primary tumours and metastatic lesions. These findings might inform the development of therapies that target different branches of Wnt signalling at specific stages of metastasis.

Automated summary

Using a unique intravital imaging platform and fluorescent reporters, researchers visualised the activities of D-catenin/TCF-dependent and ATF2-dependent signalling during cancer cell invasion, intravasation and metastatic lesion formation. They found that cancer cells easily shifted between low and high canonical Wnt activity states. Cancer cells with low Wnt canonical activity showed higher invasion and intravasation potential, while cancer cells with low ATF2-dependent activity were less invasive. Simultaneous visualisation of both reporters confirmed their complementary activities in primary tumours and metastatic lesions. These findings may inform the development of targeted therapies for different stages of metastasis by targeting different branches of Wnt signalling.