PT  - JOURNAL ARTICLE
AU  - L. Perrin
AU  - E. Belova
AU  - B. Bayarmagnai
AU  - E. Tüzel
AU  - B. Gligorijevic
TI  - Invadopodia enable cooperative invasion and metastasis of breast cancer cells
AID  - 10.1101/2021.02.13.431047
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.02.13.431047
4099  - http://biorxiv.org/content/early/2022/04/08/2021.02.13.431047.short
4100  - http://biorxiv.org/content/early/2022/04/08/2021.02.13.431047.full
AB  - Invasive and non-invasive cancer cells can invade together during the cooperative invasion. However, the events leading to it, role of EMT and the consequences this may have on metastasis are unknown. In this study, we demonstrate that the isogenic 4T1 and 67NR breast cancer cells sort from each other in 3D spheroids, followed by cooperative invasion. By time-lapse microscopy, we show that the invasive 4T1 cells move more persistently compared to non-invasive 67NR, sorting and accumulating at the spheroid-ECM interface, a process dependent on cell-ECM adhesions and independent from E-cadherin cell-cell adhesions. Elimination of invadopodia in 4T1 cells blocks invasion, demonstrating that invadopodia requirement is limited to leader cells. Importantly, we demonstrate that cells with and without invadopodia can also engage in cooperative metastasis in preclinical mouse models. Altogether, our results suggest that a small number of cells with invadopodia can drive the metastasis of heterogeneous cell clusters.Competing Interest StatementThe authors have declared no competing interest.