Tumor invasiveness is regulated by the concerted function of APC, formins, and Arp2/3 complex.
Por:
Baro L, Almhassneh RA, Islam A and Juanes MA
Publicada:
17 may 2024
Ahead of Print:
1 abr 2024
Resumen:
Tumor cell invasion is the initial step in metastasis, the leading cause of death from cancer. Invasion requires protrusive cellular structures that steer the migration of leader cells emanating from the tumor mass toward neighboring tissues. Actin is central to these processes and is therefore the prime target of drugs known as migrastatics. However, the broad effects of general actin inhibitors limit their therapeutic use. Here, we delineate the roles of specific actin nucleators in tuning actin-rich invasive protrusions and pinpoint potential pharmacological targets. We subject colorectal cancer spheroids embedded in collagen matrix-a preclinical model mirroring solid tumor invasiveness-to pharmacologic and/or genetic treatment of specific actin arrays to assess their roles in invasiveness. Our data reveal coordinated yet distinct involvement of actin networks nucleated by adenomatous polyposis coli, formins, and actin-related protein 2/3 complex in the biogenesis and maintenance of invasive protrusions. These findings may open avenues for better targeted therapies.
Filiaciones:
Baro L:
Cytoskeletal Dynamics in Cell Migration and Cancer Invasion Laboratory, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
School of Health and Life Sciences, Teesside University, Middlesbrough TS1 3BX, UK
National Horizons Centre, Teesside University, Darlington DL1 1HG, UK
Almhassneh RA:
Cytoskeletal Dynamics in Cell Migration and Cancer Invasion Laboratory, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
Islam A:
School of Health and Life Sciences, Teesside University, Middlesbrough TS1 3BX, UK
National Horizons Centre, Teesside University, Darlington DL1 1HG, UK
:
Cytoskeletal Dynamics in Cell Migration and Cancer Invasion Laboratory, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
School of Health and Life Sciences, Teesside University, Middlesbrough TS1 3BX, UK
National Horizons Centre, Teesside University, Darlington DL1 1HG, UK
Green Published, gold, Green Submitted
|