Wnt signalling is 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. Using a unique intravital imaging platform and fluorescent reporters, we visualised Wnt/β-catenin/TCF/LEF-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 may inform the development of therapies that target different branches of Wnt signalling at specific stages of metastasis.
Intravital imaging of Wnt/β-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis
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- Funder(s): Ministerio de Ciencia e Innovacion
- Award Id(s): SAF2017-84092-R
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Konstantin Stoletov, Saray Sanchez, Irantzu Gorroño, Miriam Rabano, Maria Vivanco, Robert Kypta, John D. Lewis; Intravital imaging of Wnt/β-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis. J Cell Sci 2023; jcs.260285. doi: https://doi.org/10.1242/jcs.260285
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