Faculty Opinions recommendation of Role of focal adhesions and mechanical stresses in the formation and progression of the lamellipodium-lamellum interface [corrected].

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.

Download Full-text

Microinjection of antibodies against talin inhibits the spreading and migration of fibroblasts

Journal of Cell Science ◽

10.1242/jcs.102.4.753 ◽

1992 ◽

Vol 102 (4) ◽

pp. 753-762

Author(s):

G.H. Nuckolls ◽

L.H. Romer ◽

K. Burridge

Keyword(s):

Extracellular Matrix ◽

Tissue Culture ◽

Actin Filaments ◽

Focal Adhesions ◽

Cell Spreading ◽

And Migration ◽

Extracellular Matrix Receptors

Talin is believed to be one of the key proteins involved in linking actin filaments to extracellular matrix receptors in focal adhesions. Our strategy for studying the function of talin has been to inactivate talin in living fibroblasts in tissue culture through the microinjection of affinity-purified, polyclonal anti-talin antibodies. The effect of the injected anti-talin antibodies on cell spreading was found to depend on how recently the cells had been plated. Cells that were in the process of spreading on a fibronectin substratum, and which had newly developed focal adhesions, were induced to round up and to disassemble many of the adhesions. However, if fibroblasts were allowed to spread completely before they were microinjected with the anti-talin antibody, focal adhesions remained intact and the flat morphology of the cells was unaffected. The percentage of cells that were able to maintain a spread morphology despite the injection of anti-talin antibodies increased during the first few hours after plating on fibronectin substrata. Fibroblasts that were allowed to spread completely before microinjection with the anti-talin antibody retained both intact focal adhesions and a flat, well-spread morphology, but failed to migrate effectively. Our experiments do not directly address the role of talin in mature focal adhesions, but they indicate that talin is essential for the spreading and migration of fibroblasts on fibronectin as well as for the development and initial maintenance of focal adhesions on this substratum.

Download Full-text

Role of interaction with vinculin in recruitment of vinexins to focal adhesions

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2005.08.064 ◽

2005 ◽

Vol 336 (1) ◽

pp. 239-246 ◽

Cited By ~ 25

Author(s):

Honami Takahashi ◽

Masaru Mitsushima ◽

Naoya Okada ◽

Takuya Ito ◽

Sanae Aizawa ◽

...

Keyword(s):

Focal Adhesions

Download Full-text

Multifaceted role of tensins in cancer

10.7287/peerj.preprints.27990 ◽

2019 ◽

Author(s):

Abdulaziz Alfahed ◽

Teresa P Raposo ◽

Mohammad Ilyas

Keyword(s):

Cancer Biology ◽

Focal Adhesions ◽

Adaptor Proteins ◽

Therapeutic Strategies ◽

Cell Behavior ◽

Surrounding Environment ◽

Signaling Mechanisms ◽

Different Types ◽

Biochemical Signals

Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.

Download Full-text

High Plasma Levels of Soluble Talin-1 in Patients with Coronary Artery Disease

Disease Markers ◽

10.1155/2020/2479830 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Masayuki Aoyama ◽

Yoshimi Kishimoto ◽

Emi Saita ◽

Yukinori Ikegami ◽

Reiko Ohmori ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Vessels ◽

Focal Adhesions ◽

High Plasma ◽

Blood Levels ◽

Atherosclerotic Plaques ◽

Vessel Disease ◽

Artery Disease

Aims. Talin-1 is a cytoskeletal protein that binds integrin, thereby leading to integrin activation and affecting focal adhesions. Recently, talin-1 expression was reported to be downregulated in human atherosclerotic plaques. However, blood levels of soluble talin-1 (sTalin-1) in patients with atherosclerotic disease, such as coronary artery disease (CAD), have not been elucidated. Methods. We measured plasma sTalin-1 levels in 349 patients undergoing elective coronary angiography. The severity of CAD was represented as the number of stenotic coronary vessels and segments. Results. Of the 349 study patients, CAD was found in 194 patients, of whom 88 had 1-vessel disease (1-VD), 60 had 2-vessel disease (2-VD), and 46 had 3-vessel disease (3-VD). Plasma sTalin-1 levels were higher in 194 patients with CAD than in 155 without CAD (CAD(-) group) (median 0.30 vs. 0.23 ng/mL, P<0.005). A stepwise increase in sTalin-1 levels was found depending on the number of >50% stenotic coronary vessels: 0.23 in CAD(-), 0.29 in 1-VD, 0.30 in 2-VD, and 0.32 ng/mL in 3-VD group, respectively, (P<0.05). High sTalin-1 level (>0.28 ng/mL) was found in 36% of CAD(-), 51% of 1-VD, 53% of 2-VD, and 59% of 3-VD group (P<0.025). sTalin-1 levels also correlated with the number of >50% stenotic segments (r=0.14, P<0.02). The multivariate analysis revealed that sTalin-1 levels were independently associated with CAD. The odds ratio for CAD was 1.83 (95%CI=1.14−2.93) for high sTalin-1 level (>0.28 ng/mL) (P<0.02). Conclusions. Plasma sTalin-1 levels in patients with CAD were found to be high and to be associated with the presence and severity of CAD, suggesting a role of sTalin-1 in the progression of coronary atherosclerosis.

Download Full-text

The role of embryo contact and focal adhesions during maternal recognition of pregnancy

PLoS ONE ◽

10.1371/journal.pone.0213322 ◽

2019 ◽

Vol 14 (3) ◽

pp. e0213322 ◽

Cited By ~ 2

Author(s):

K. M. Klohonatz ◽

L. C. Nulton ◽

A. M. Hess ◽

G. J. Bouma ◽

J. E. Bruemmer

Keyword(s):

Focal Adhesions ◽

Maternal Recognition Of Pregnancy

Download Full-text

Alignment of Carbon Nanotubes: An Approach to Modulate Cell Orientation and Asymmetry

Nano LIFE ◽

10.1142/s1793984414500020 ◽

2014 ◽

Vol 04 (01) ◽

pp. 1450002 ◽

Cited By ~ 1

Author(s):

Qingsu Cheng ◽

Greg M. Harris ◽

Marc-Olivier Blais ◽

Katy Rutledge ◽

Ehsan Jabbarzadeh

Keyword(s):

Stem Cells ◽

Control Cell ◽

Adhesion Formation ◽

Embryonic Stem ◽

Focal Adhesions ◽

Biological Tissues ◽

Spatiotemporal Pattern ◽

Cell Alignment ◽

Cell Orientation

Stem cells offer a promising tool in tissue engineering strategies, as their differentiated derivatives can be used to reconstruct most biological tissues. These approaches rely on controlling the biophysical cues that tune the ultimate fate of cells. In this context, significant effort has gone to parse out the role of conflicting matrix-elicited signals (e.g., topography and elasticity) in regulation of macroscopic characteristics of cells (e.g., shape and polarity). A critical hurdle, however, lies in our inability to recapitulate the nanoscale spatiotemporal pattern of these signals. The study presented in this manuscript took an initial step to overcome this challenge by developing a carbon nanotube (CNT)-based substrate for nanoresolution control of focal adhesion formation and cell alignment. The utility of this system was studied using human umbilical vascular endothelial cells (HUVECs) and human embryonic stem cells (hESCs) at a single cell level. Our results demonstrated the ability to control cell orientation by merely controlling the alignment of focal adhesions at a nanoscale size. Our long-term vision is to use these nanoengineered substrates to mimic cell orientation in earlier development and explore the role of polarity in asymmetric division and lineage specification of dividing cells.

Download Full-text

Force-dependent vinculin binding to talin in live cells: a crucial step in anchoring the actin cytoskeleton to focal adhesions

AJP Cell Physiology ◽

10.1152/ajpcell.00122.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. C607-C620 ◽

Cited By ~ 57

Author(s):

Hiroaki Hirata ◽

Hitoshi Tatsumi ◽

Chwee Teck Lim ◽

Masahiro Sokabe

Keyword(s):

Actin Cytoskeleton ◽

Focal Adhesions ◽

Living Cells ◽

Live Cells ◽

Mechanical Forces ◽

Actin Network ◽

Crucial Step

Mechanical forces play a pivotal role in the regulation of focal adhesions (FAs) where the actin cytoskeleton is anchored to the extracellular matrix through integrin and a variety of linker proteins including talin and vinculin. The localization of vinculin at FAs depends on mechanical forces. While in vitro studies have demonstrated the force-induced increase in vinculin binding to talin, it remains unclear whether such a mechanism exists at FAs in vivo. In this study, using fibroblasts cultured on elastic silicone substrata, we have examined the role of forces in modulating talin-vinculin binding at FAs. Stretching the substrata caused vinculin accumulation at talin-containing FAs, and this accumulation was abrogated by expressing the talin-binding domain of vinculin (domain D1, which inhibits endogenous vinculin from binding to talin). These results indicate that mechanical forces loaded to FAs facilitate vinculin binding to talin at FAs. In cell-protruding regions, the actin network moved backward over talin-containing FAs in domain D1-expressing cells while it was anchored to FAs in control cells, suggesting that the force-dependent vinculin binding to talin is crucial for anchoring the actin cytoskeleton to FAs in living cells.

Download Full-text