APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

Lautaro Baro; Asifa Islam; Hannah m. Brown; Zoë a. Bell; M. angeles Juanes

doi:10.1016/j.isci.2023.106583

APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

Lautaro Baro, Asifa Islam, Hannah m. Brown, Zoë a. Bell, M. angeles Juanes

Research output: Contribution to journal › Article › peer-review

Abstract

Cell remodeling relies on dynamic rearrangements of cell contacts powered by the actin cytoskeleton. The tumor suppressor adenomatous polyposis coli (APC) nucleate actin filaments (F-actin) and localizes at cell junctions. Whether APC-driven actin nucleation acts in cell junction remodeling remains unknown. By combining bioimaging and genetic tools with artificial intelligence algorithms applied to colorectal cancer cell, we found that the APC-dependent actin pool contributes to sustaining levels of F-actin, as well as E-cadherin and occludin protein levels at cell junctions. Moreover, this activity preserved cell junction length and angle, as well as vertex motion and integrity. Loss of this F-actin pool led to larger cells with slow and random cell movement within a sheet. Our findings suggest that APC-driven actin nucleation promotes cell junction integrity and dynamics to facilitate collective cell remodeling and motility. This offers a new perspective to explore the relevance of APC-driven cytoskeletal function in gut morphogenesis.

Original language	English
Article number	106583
Journal	iScience
Volume	26
Issue number	5
DOIs	https://doi.org/10.1016/j.isci.2023.106583
Publication status	Published - 6 Apr 2023

Bibliographical note

This work was supported by grants from the Academy of Medical Science/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award [SBF006∖1070], and the CIDEGENT Excellent Research Program of the Valencian regional government Plan GenT/CIDEGENT/2021/026 to M.A.J. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020). L.B. was supported by a fully funded PhD studentship by Teesside University.

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https://linkinghub.elsevier.com/retrieve/pii/S2589004223006600

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title = "APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells",

abstract = "Cell remodeling relies on dynamic rearrangements of cell contacts powered by the actin cytoskeleton. The tumor suppressor adenomatous polyposis coli (APC) nucleate actin filaments (F-actin) and localizes at cell junctions. Whether APC-driven actin nucleation acts in cell junction remodeling remains unknown. By combining bioimaging and genetic tools with artificial intelligence algorithms applied to colorectal cancer cell, we found that the APC-dependent actin pool contributes to sustaining levels of F-actin, as well as E-cadherin and occludin protein levels at cell junctions. Moreover, this activity preserved cell junction length and angle, as well as vertex motion and integrity. Loss of this F-actin pool led to larger cells with slow and random cell movement within a sheet. Our findings suggest that APC-driven actin nucleation promotes cell junction integrity and dynamics to facilitate collective cell remodeling and motility. This offers a new perspective to explore the relevance of APC-driven cytoskeletal function in gut morphogenesis.",

author = "Lautaro Baro and Asifa Islam and Brown, {Hannah m.} and Bell, {Zo{\"e} a.} and Juanes, {M. angeles}",

note = "This work was supported by grants from the Academy of Medical Science/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award [SBF006∖1070], and the CIDEGENT Excellent Research Program of the Valencian regional government Plan GenT/CIDEGENT/2021/026 to M.A.J. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020). L.B. was supported by a fully funded PhD studentship by Teesside University.",

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AU - Baro, Lautaro

AU - Islam, Asifa

AU - Brown, Hannah m.

AU - Bell, Zoë a.

AU - Juanes, M. angeles

N1 - This work was supported by grants from the Academy of Medical Science/the Wellcome Trust/the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award [SBF006∖1070], and the CIDEGENT Excellent Research Program of the Valencian regional government Plan GenT/CIDEGENT/2021/026 to M.A.J. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020). L.B. was supported by a fully funded PhD studentship by Teesside University.

PY - 2023/4/6

Y1 - 2023/4/6

N2 - Cell remodeling relies on dynamic rearrangements of cell contacts powered by the actin cytoskeleton. The tumor suppressor adenomatous polyposis coli (APC) nucleate actin filaments (F-actin) and localizes at cell junctions. Whether APC-driven actin nucleation acts in cell junction remodeling remains unknown. By combining bioimaging and genetic tools with artificial intelligence algorithms applied to colorectal cancer cell, we found that the APC-dependent actin pool contributes to sustaining levels of F-actin, as well as E-cadherin and occludin protein levels at cell junctions. Moreover, this activity preserved cell junction length and angle, as well as vertex motion and integrity. Loss of this F-actin pool led to larger cells with slow and random cell movement within a sheet. Our findings suggest that APC-driven actin nucleation promotes cell junction integrity and dynamics to facilitate collective cell remodeling and motility. This offers a new perspective to explore the relevance of APC-driven cytoskeletal function in gut morphogenesis.

AB - Cell remodeling relies on dynamic rearrangements of cell contacts powered by the actin cytoskeleton. The tumor suppressor adenomatous polyposis coli (APC) nucleate actin filaments (F-actin) and localizes at cell junctions. Whether APC-driven actin nucleation acts in cell junction remodeling remains unknown. By combining bioimaging and genetic tools with artificial intelligence algorithms applied to colorectal cancer cell, we found that the APC-dependent actin pool contributes to sustaining levels of F-actin, as well as E-cadherin and occludin protein levels at cell junctions. Moreover, this activity preserved cell junction length and angle, as well as vertex motion and integrity. Loss of this F-actin pool led to larger cells with slow and random cell movement within a sheet. Our findings suggest that APC-driven actin nucleation promotes cell junction integrity and dynamics to facilitate collective cell remodeling and motility. This offers a new perspective to explore the relevance of APC-driven cytoskeletal function in gut morphogenesis.

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APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

Abstract

Bibliographical note

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