Abstract
Collective cell migration is essential in early development, morphogenesis, tissue
regeneration, wound healing, and cancer metastasis. Collective cell migration depends on fine-tuning remodeling between neighbor cells coupled to a dynamic actin cytoskeleton. Mutations or alterations in the tumor suppressor Adenomatous Polyposis Coli (APC), most of which result in truncated products, have been found in >80% of colorectal cancer cases. APC plays a role in cell migration through its interactions with the cytoskeleton. Previously we showed that APC nucleates actin filaments in cells, and this activity promotes microtubule-induced focal adhesion turnover to facilitate directionality of individual cells on a culture dish. In addition, APC has been found at the cell junctions in epithelial monolayers. However, whether APC-driven actin activity contributes to any collective cell migration event in gut homeostasis and/or impacts on health is unknown. To start to investigate this paradigm, here we have used epithelial monolayers and preclinical 3D models expressing stable APC-m4 - a separation-offunction mutant of APC incapable to nucleate actin. Using live cell imaging we have observed that lack of actin generated by APC significantly alters the organization and directionality of cells in wounded epithelial monolayers. In addition to those parameters, we have also visualized that the invasive behavior of the colorectal cancer 3D models expressing APC-m4 is largely compromised. These results suggest that
APC-driven actin nucleation function is critical to control physiological and pathological migratory processes, including cell remodeling and tumor dissemination. Our findings offer a new perspective to explore the relevance of APC-driven cytoskeletal functions in gut morphogenesis and human disease.
regeneration, wound healing, and cancer metastasis. Collective cell migration depends on fine-tuning remodeling between neighbor cells coupled to a dynamic actin cytoskeleton. Mutations or alterations in the tumor suppressor Adenomatous Polyposis Coli (APC), most of which result in truncated products, have been found in >80% of colorectal cancer cases. APC plays a role in cell migration through its interactions with the cytoskeleton. Previously we showed that APC nucleates actin filaments in cells, and this activity promotes microtubule-induced focal adhesion turnover to facilitate directionality of individual cells on a culture dish. In addition, APC has been found at the cell junctions in epithelial monolayers. However, whether APC-driven actin activity contributes to any collective cell migration event in gut homeostasis and/or impacts on health is unknown. To start to investigate this paradigm, here we have used epithelial monolayers and preclinical 3D models expressing stable APC-m4 - a separation-offunction mutant of APC incapable to nucleate actin. Using live cell imaging we have observed that lack of actin generated by APC significantly alters the organization and directionality of cells in wounded epithelial monolayers. In addition to those parameters, we have also visualized that the invasive behavior of the colorectal cancer 3D models expressing APC-m4 is largely compromised. These results suggest that
APC-driven actin nucleation function is critical to control physiological and pathological migratory processes, including cell remodeling and tumor dissemination. Our findings offer a new perspective to explore the relevance of APC-driven cytoskeletal functions in gut morphogenesis and human disease.
| Original language | English |
|---|---|
| Publication status | Published - 16 May 2022 |
| Event | European Cytoskeletal Forum Meeting 2022 - Hannover, Hannover, Germany Duration: 16 May 2022 → 19 May 2022 https://www.europeancytoskeletalforum.org/scientific-programm-ecf-2022 |
Conference
| Conference | European Cytoskeletal Forum Meeting 2022 |
|---|---|
| Abbreviated title | ECF2022 |
| Country/Territory | Germany |
| City | Hannover |
| Period | 16/05/22 → 19/05/22 |
| Internet address |