The actin cytoskeleton: Morphological changes in pre- and fully developed lung cancer

Arkaprabha Basu, Manash K. Paul, Shimon Weiss

Research output: Contribution to journalReview articlepeer-review

Abstract

Actin, a primary component of the cell cytoskeleton can have multiple isoforms, each of which can have specific properties uniquely suited for their purpose. These monomers are then bound together to form polymeric filaments utilizing adenosine triphosphate hydrolysis as a source of energy. Proteins, such as Arp2/3, VASP, formin, profilin, and cofilin, serve important roles in the polymerization process. These filaments can further be linked to form stress fibers by proteins called actin-binding proteins, such as α-actinin, myosin, fascin, filamin, zyxin, and epsin. These stress fibers are responsible for mechanotransduction, maintaining cell shape, cell motility, and intracellular cargo transport. Cancer metastasis, specifically epithelial mesenchymal transition (EMT), which is one of the key steps of the process, is accompanied by the formation of thick stress fibers through the Rho-associated protein kinase, MAPK/ERK, and Wnt pathways. Recently, with the advent of “field cancerization,” pre-malignant cells have also been demonstrated to possess stress fibers and related cytoskeletal features. Analytical methods ranging from western blot and RNA-sequencing to cryo-EM and fluorescent imaging have been employed to understand the structure and dynamics of actin and related proteins including polymerization/depolymerization. More recent methods involve quantifying properties of the actin cytoskeleton from fluorescent images and utilizing them to study biological processes, such as EMT. These image analysis approaches exploit the fact that filaments have a unique structure (curvilinear) compared to the noise or other artifacts to separate them. Line segments are extracted from these filament images that have assigned lengths and orientations. Coupling such methods with statistical analysis has resulted in development of a new reporter for EMT in lung cancer cells as well as their drug responses.

Original languageEnglish
Article number041304
JournalBiophysics Reviews
Volume3
Issue number4
DOIs
StatePublished - 1 Dec 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 Author(s).

Funding

The research was supported by the STROBE National Science Foundation Science and Technology Center (Grant No. DMR-1548924) and Willard Chair funds.

FundersFunder number
STROBE National Science Foundation Science and Technology CenterDMR-1548924

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