Cell Adhesion & Migration最新文献

Fluid shear stress (FSS) regulates the metastasis of hepatocellular carcinoma (HCC). In the present study, we aimed to study the role of autophagy in HCC cells under FSS. The results showed that FSS upregulated the protein markers of autophagy, induced LC3B aggregation and formation of autophagosomes. Inhibition of integrin by Cliengitide (Cli) or inhibition of the microfilaments formation both inhibited the activation of autophagy in HepG2 under FSS. In addition, Cli inhibited the microfilaments formation and expressions of Rac1 and RhoA in HepG2 cells under FSS. Finally, inhibition of autophagy suppressed the cell migration and invasion in HepG2 under FSS. In conclusion, FSS induced autophagy to promote migration and invasion of HepG2 cells via integrin/cytoskeleton pathways.

Cell migration is highly sensitive to fluid shear stress (FSS) in blood flow or interstitial fluid flow. However, whether the FSS gradient can regulate the migration of cells remains unclear. In this work, we constructed a parallel-plate flow chamber with different FSS gradients and verified the gradient flow field by particle image velocimetry measurements and finite element analyses. We then investigated the effect of FSS magnitudes and gradients on the migration of osteoclast precursor RAW264.7 cells. Results showed that the cells sensed the FSS gradient and migrated toward the low-FSS region. This FSS gradient-induced migration tended to occur in low-FSS magnitudes and high gradients, e.g., the migration angle relative to flow direction was approximately 90° for 0.1 Pa FSS and 0.2 Pa mm^-1 FSS gradient. When chemically inhibiting the calcium signaling pathways of the mechanosensitive cation channel, endoplasmic reticulum, phospholipase C, and extracellular calcium, the cell migration toward the low-FSS region was significantly reduced. This study may provide insights into the mechanism of the recruitment of osteoclast precursors at the site of bone resorption and of mechanical stimulation-induced bone remodeling.

Hyaluronic acid (HA) preparations are widely used in clinical practice and recent data suggest that commercially available HA-based compounds promote ulcer re-epithelialization and induce pain relief. However, the pathophysiological basis of these effects remains poorly understood. In the present study, we investigated the biophysical, biomolecular and functional properties of a HA preparation combined with a pool of collagen precursor synthetic aminoacids, namely l-proline, l-leucine, l-lysine and glycine (Aminogam®). Hydrodynamic characterization of Aminogam® by size exclusion chromatography-triple detector array (SEC-TDA) revealed an average molecular weight in the range of 700-1700 kDa. Rheological measurements of the 1700kDa M_w lot showed a pseoudoplastic behaviour with a zero-shear viscosity (η₀) equal to 90 ± 9 Pa∙s at 25°C and 55 ± 6 Pa∙s at 37°C. Automated time-lapse videomicroscopy studies in a fibroblast-free system demonstrated that 1% (v/v) Aminogam® significantly reduced the healing time of wounded keratinocyte monolayers. In AKGOS assays, Aminogam® stimulated cellular locomotion (chemokinesis) and directional migration (chemotaxis) of keratinocytes. Analysis of microarray data suggested that keratinocytes had a functional neuroendocrine machinery, and this was confirmed by testing the secretion of six neuroactive molecules by ELISA, namely α-MSH, β-endorphins, melatonin, substance P, cortisol, and neurotensin. Interestingly, Aminogam® regulated the production of several neuropeptides, including β-endorphins. In conclusion, our data shed light on the epithelial-dependent mechanisms that underlie the efficacy of Aminogam®, particularly in reference to wound healing and nociception.

The epithelial mesenchymal transition (EMT) is one step in the process through which carcinoma cells metastasize by gaining the cellular mobility associated with mesenchymal cells. This work examines the dual influence of the TGF-β pathway and intercellular contact on the activation of EMT in colon (SW480) and breast (MCF7) carcinoma cells. While the SW480 population revealed an intermediate state between the epithelial and mesenchymal states, the MC7 cells exhibited highly adhesive behavior. However, for both cell lines, an exogenous TGF-β signal and a reduction in cellular confluence can push a subgroup of the population towards the mesenchymal phenotype. Together, these results highlight that, while EMT is induced by the synergy of multiple signals, this activation varies across cell types.

The actin cytoskeleton of hepatic stellate cells (HSCs) is reorganized when they are cultured in 3D collagen matrices. Here, we investigated the molecular mechanism of actin cytoskeleton reorganization in HSCs cultured in 3D floating collagen matrices (FCM) compared to those on 2D polystyrene surfaces (PS). First, we found that the generation of dendritic cellular processes was controlled by Rac1. Next, we examined the differential gene expression of HSCs cultured on 2D PS and in 3D FCM by RNA-Seq and focused on the changes of actin cytoskeleton reorganization-related molecular components and guanine nucleotide exchange factors (GEFs). The results showed that the expression of genes associated with actin cytoskeleton reorganization-related cellular components, filopodia and lamellipodia, were significantly decreased, but podosome-related genes was significantly increased in 3D FCM. Furthermore, we found that a Rac1-specific GEF, ARHGEF4, played roles in morphological changes, migration and podosome-related gene expression in HSCs cultured in 3D FCM. Abbreviations: 2D PS: 2-dimensional polystyrene surface; 3D FCM: 3-dimensional floating collagen matrices; ARHGEF4: Rho guanine nucleotide exchange factor 4; ARHGEF6: Rho guanine nucleotide exchange factor 6; GEF: guanine nucleotide exchange factor; HSC: hepatic stellate cell.

Snail2 is a repressor of E-cadherin during carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here, we determined that Snail2 was highly increased during TGF-β-induced EMT process in lung cells. H3K9 methylation was up-regulated and H3K4/H3K56 acetylation were down-regulated at the E-cadherin promoter. Snail2 interacted with G9a and HDACs to exert suppression of E-cadherin transcription. Overexpression of Snail2 enhanced the migration and invasion ability, whereas G9a and HDACs inhibition significantly reversed this effect. Our study demonstrated the importance of G9a- and HDACs-mediated regulation during Snail2-induced E-cadherin repression and metastasis during LC progression.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. It arises during development of the sympathetic nervous system. Netrin-4 (NTN4), a laminin-related protein, has been proposed as a key factor to target NB metastasis, although there is controversy about its function. Here, we show that NTN4 is broadly expressed in tumor, stroma and blood vessels of NB patient samples. Furthermore, NTN4 was shown to act as a cell adhesion molecule required for the migration induced by Neogenin-1 (NEO1) in SK-N-SH neuroblastoma cells. Therefore, we propose that NTN4, by forming a ternary complex with Laminin γ1 (LMγ1) and NEO1, acts as an essential extracellular matrix component, which induces the migration of SK-N-SH cells.

The role of hyaluronan (HA) in periodontal healing has been speculated via its interaction with the CD44 receptor. While HA-CD44 interactions have previously been implicated in numerous cell types; effect and mechanism of exogenous HA on periodontal ligament (PDL) cells is less clear. Herein, we examine the effect of exogenous HA on contractility and migration in human and murine PDL cells using arrays of microposts and time-lapse microscopy. Our findings observed HA-treated human PDL cells as more contractile and less migratory than untreated cells. Moreover, the effect of HA on contractility and focal adhesion area was abrogated when PDL cells were treated with Y27632, an inhibitor of rho-dependent kinase, but not when these cells were treated with ML-7, an inhibitor of myosin light chain kinase. Our results provide insight into the mechanobiology of PDL cells, which may contribute towards the development of therapeutic strategies for periodontal healing and tissue regeneration.

Colorectal cancer has a common cause of morbidity and mortality. Therefore, it is urgent to detect reliable biomarkers to predict prognosis in CRC. Here, we determined the expression of TIMP-2 and MMP-9 in a  CRC tissue microarray by immunohistochemistry. We found that lower TIMP-2 or/and higher MMP-9 expression in cancer tissues was correlated with poorer overall survival (OS). TIMP-2 or MMP-9 expression was independent prognostic factors for CRC. Furthermore, TIMP-2 and MMP-9 expression had a synergistic role as efficient prognostic indicators for CRC patients. In vitro and in vivo, TIMP-2 could inhibit HCT 116 cells invasion and migration by regulating MMP-9. In sum, a combined expression of TIMP-2 and MMP-9 as efficient prognostic indicators was found for the first time.

Cell migration is a highly orchestrated cellular event that involves physical interactions of diverse subcellular components. The nucleus as the largest and stiffest organelle in the cell not only maintains genetic functionality, but also actively changes its morphology and translocates through dynamic formation of nucleus-bound contractile stress fibers. Nuclear motion is an active and essential process for successful cell migration and nucleus self-repairs in response to compression and extension forces in complex cell microenvironment. This review recapitulates molecular regulators that are crucial for nuclear motility during cell migration and highlights recent advances in nuclear deformation-mediated rupture and repair processes in a migrating cell.