Physical biology in cancer. 5. The rocky road of metastasis: the role of cytoskeletal mechanics in cell migratory response to 3D matrix topography - PubMed (original) (raw)

Review

Physical biology in cancer. 5. The rocky road of metastasis: the role of cytoskeletal mechanics in cell migratory response to 3D matrix topography

Francois Bordeleau et al. Am J Physiol Cell Physiol. 2014.

Abstract

The tumor microenvironment is a milieu of heterogeneous architectural features that affect tumor growth and metastatic invasion. Pore size, density, stiffness, and fiber architecture change dramatically from location to location throughout the tumor matrix. While many studies have addressed the effects of two-dimensional extracellular matrix structure and composition on cell migration, less is known about how cancer cells navigate complex, heterogeneous three-dimensional (3D) microenvironments. Mechanical structures such as actin and keratin, part of the cytoskeletal framework, and lamins, part of the nucleoskeletal framework, play a key role in migration and are altered during cancer progression. Recent evidence suggests that these changes in cytoskeletal and nucleoskeletal structures may enable cancer cells to efficiently respond to features such as pore size and stiffness to invade and migrate. Here we discuss the role of cell mechanics and the cytoskeleton in the ability of cells to navigate and respond to 3D matrix features and heterogeneities.

Keywords: actin; cytoskeleton; extracellular matrix topography; keratin; lamins; mechanosensing; nucleoskeleton; three-dimensional migration.

PubMed Disclaimer

Figures

Fig. 1.

Fig. 1.

Overview of key mechanical features governing cell migration in restrictive 3-dimensional (3D) channels. A: representations of the same migrating cell inside a restrictive 3D channel showing cortical localization of actin along the wall of the channel and at both extremities of the migrating cell, intermediate filament (IF) localization at the leading edge of the migrating cell, microtubule (MT) preferential localization at the leading edge of the migrating cell, and a schematic of cytoskeletal-nucleoskeletal connections via linker of nucleoskeleton and cytoskeleton (LINC) complex coupling of lamins and actin/IFs. B: overexpression of lamin IFs stiffens the nucleus and poses a significant barrier to migration in subnuclear pore sizes, while diminished expression of lamin IFs softens the nucleus and allows for greater nuclear deformability. C: confocal image of a cell migrating inside a microfabricated 3D collagen microtrack showing actin (green) and reflectance (collagen, cyan). (See Ref. for details.)

Fig. 2.

Fig. 2.

A migrating cell relies on the coordinated effort of the cytoskeleton for its mechanosensing ability in a 3D matrix. A migrating cell utilizes the polarizing features of the MT network while also relying on IF assembly and localization at the leading edge to initiate integrin binding (A). When the migrating cell reaches a stiffened interface (arrow), it has the potential to initiate localized integrin binding sites, as well as formation of stress fibers and nuclear deformation, changing the overall cell morphology to a spread shape (B).

Similar articles

Cited by

References

    1. Alam H, Gangadaran P, Bhate AV, Chaukar DA, Sawant SS, Tiwari R, Bobade J, Kannan S, D'Cruz AK, Kane S, Vaidya MM. Loss of keratin 8 phosphorylation leads to increased tumor progression and correlates with clinico-pathological parameters of OSCC patients. PLos One 6: e27767, 2011 - PMC - PubMed
    1. Alam H, Kundu ST, Dalal SN, Vaidya MM. Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line. J Cell Sci 124: 2096–2106, 2011 - PubMed
    1. Antonyak MA, Li B, Regan AD, Feng Q, Dusaban SS, Cerione RA. Tissue transglutaminase is an essential participant in the epidermal growth factor-stimulated signaling pathway leading to cancer cell migration and invasion. J Biol Chem 284: 17914–17925, 2009 - PMC - PubMed
    1. Balzer EM, Tong Z, Paul CD, Hung WC, Stroka KM, Boggs AE, Martin SS, Konstantopoulos K. Physical confinement alters tumor cell adhesion and migration phenotypes. FASEB J 26: 4045–4056, 2012 - PMC - PubMed
    1. Bhattacharya R, Gonzalez AM, Debiase PJ, Trejo HE, Goldman RD, Flitney FW, Jones JC. Recruitment of vimentin to the cell surface by β3-integrin and plectin mediates adhesion strength. J Cell Sci 122: 1390–1400, 2009 - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources