Tumor invasiveness is regulated by the concerted function of APC, formins, and Arp2/3 complex

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...

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Bibliographic Details
Published iniScience Vol. 27; no. 5; p. 109687
Main Authors Baro, Lautaro, Almhassneh, Rabeah A., Islam, Asifa, Juanes, M. Angeles
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 17.05.2024
Subjects
Biochemistry
Biological sciences
Cancer systems biology
Cell biology
Natural sciences
Systems biology
Cell biology
Cancer systems biology
Biochemistry
Biological sciences
Natural sciences
Systems biology
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Summary: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. [Display omitted] •APC-driven actin nucleation plays a role in the formation of invasive protrusions•Different actin nucleators coordinate the biogenesis of invasive protrusion•Formins and Arp2/3 complex do not participate in the maintenance of matured protrusions•Dynamics of leader cells emanating from spheroids depends on actin nucleated by APC Biochemistry; Biological sciences; Cancer systems biology; Cell biology; Natural sciences; Systems biology
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109687