Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream Rac1 signaling

Guillou, Hervé; Depraz-Depland, Adeline; Planus, Emmanuelle; Vianay, Benoît; Chaussy, Jacques; Grichine, Alexeï; Albigès-Rizo, Corinne; Block, Marc R.

doi:10.1016/j.yexcr.2007.10.026

Cited by 68 publications

(68 citation statements)

References 45 publications

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“…2B). Both structures contain a large density of integrins (57) and play major roles in leading cancer cell migration and invasion (58,59). To study the cell morphological changes (lamellipodia and filopodia), a DIC microscope was used.…”

Section: Resultsmentioning

confidence: 99%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

164

113

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Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.gold nanorods | cytoskeleton | integrin | metastasis | plasmonic photothermal therapy

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Section: Resultsmentioning

confidence: 99%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

164

113

View full text Add to dashboard Cite

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“…4B). The effect of apigenin on filopodia formation may help to explain the effect on the directionality of cell movement, because inhibition of filopodia formation leads to impaired motility (41).…”

Section: And D)mentioning

confidence: 99%

The Chemopreventive Bioflavonoid Apigenin Inhibits Prostate Cancer Cell Motility through the Focal Adhesion Kinase/Src Signaling Mechanism

Franzen

Amargo

Todorović

et al. 2009

Cancer Prevention Research

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Prostate cancer mortality is primarily attributed to metastatic rather than primary, organ-confined disease. Acquiring a motile and invasive phenotype is an important step in development of tumors and ultimately metastasis. This step involves remodeling of the extracellular matrix and of cell-matrix interactions, cell movement mediated by the actin cytoskeleton, and activation of focal adhesion kinase (FAK)/Src signaling. Epidemiologic studies suggest that the metastatic behavior of prostate cancer may be an ideal target for chemoprevention. The natural flavone apigenin is known to have chemopreventive properties against many cancers, including prostate cancer. Here, we study the effect of apigenin on motility, invasion, and its mechanism of action in metastatic prostate carcinoma cells (PC3-M). We found that apigenin inhibits PC3-M cell motility in a scratchwound assay. Live cell imaging studies show that apigenin diminishes the speed and affects directionality of cell motion. Alterations in the cytoskeleton are consistent with impaired cell movement in apigenin-treated cells. Apigenin treatment leads to formation of "exaggerated filopodia," which show accumulation of focal adhesion proteins at their tips. Furthermore, apigenin-treated cells adhere more strongly to the extracellular matrix. Additionally, apigenin decreases activation of FAK and Src, and phosphorylation of Src substrates FAK Y576/577 and Y925. Expression of constitutively active Src blunts the effect of apigenin on cell motility and cytoskeleton remodeling. These results show that apigenin inhibits motility and invasion of prostate carcinoma cells, disrupts actin cytoskeleton organization, and inhibits FAK/Src signaling. These studies provide mechanistic insight into developing novel strategies for inhibiting prostate cancer cell motility and invasiveness.Prostate cancer is the most common noncutaneous malignancy in American males (over 186,000 cases diagnosed yearly), and the second leading cause of cancer-related deaths in American men (28,660 estimated deaths in 2008; ref. 1). In prostate cancer, most deaths are attributed to metastatic disease rather than primary, organ-confined prostate cancer (2-5). Numerous epidemiologic studies (6) suggest that the metastatic behavior of prostate cancer may be an ideal target for pharmacologic intervention with chemopreventive agents. Because prostate cancer is typically diagnosed in older men, chemopreventive and/or chemotherapeutic strategies to delay its progression may have a substantial impact on clinical outcome. Epidemiologic studies have shown that Asian men experience a lower incidence of metastatic prostate cancer than Western men, which is attributed to dietary and/or life-style factors (3, 4). Interestingly, some studies suggest that the incidence of primary cancer may be similar in Asian and Western populations, and that the higher rate of prostate cancer-related deaths in the United States is due to a higher rate of prostate cancer metastasis (3,5).Apigenin (4′, 5, 7-trihydroxyflavo...

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“…Using substrates with discrete adhesion sites, Guillou et al (2008) [13] experimentally revealed the complex nature of membrane protrusion. First, filopodia grow until they reach an adhesion patch.…”

Section: Cell Environmentmentioning

confidence: 99%

“…substrate or matrix rigidity manipulation) [26], geometrically (e.g. shape and pitch length of adhesive pattern) [13] or topographically (3D adhesive structures with pillars or lines) [33,35].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

On the Influence of Discrete Adhesive Patterns for Cell Shape and Motility: A Computational Approach

Franco

Tzvetkova-Chevolleau

Stéphanou

2010

Math. Model. Nat. Phenom.

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Abstract. In this paper, we propose a computational model to investigate the coupling between cell's adhesions and actin fibres and how this coupling affects cell shape and stability. To accomplish that, we take into account the successive stages of adhesion maturation from adhesion precursors to focal complexes and ultimately to focal adhesions, as well as the actin fibres evolution from growing filaments, to bundles and finally contractile stress fibres.We use substrates with discrete patterns of adhesive patches, whose inter-patches distance can be modulated in order to control the location of the adhesions and the resulting fibres architecture. We then investigate the emergence of stable cell morphologies as a function of the inter-patches distance, for two different cell phenotypes generated from the model. Force generated by the stress fibres on the focal adhesions and specifically the influence of the cell contractility are also investigated.Our results suggest that adhesion lifetime and fibre growing rate are the key parameters in the emergence of stable cell morphologies and the limiting factors for the magnitude of the mean tension force from the fibres on the focal adhesions.

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Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream Rac1 signaling

Cited by 68 publications

References 45 publications

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

The Chemopreventive Bioflavonoid Apigenin Inhibits Prostate Cancer Cell Motility through the Focal Adhesion Kinase/Src Signaling Mechanism

On the Influence of Discrete Adhesive Patterns for Cell Shape and Motility: A Computational Approach

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