Correction: Actin Cytoskeleton Regulation of Epithelial Mesenchymal Transition in Metastatic Cancer Cells.
Ontology highlight
ABSTRACT:
SUBMITTER: Shankar J
PROVIDER: S-EPMC4500445 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Correction: Actin Cytoskeleton Regulation of Epithelial Mesenchymal Transition in Metastatic Cancer Cells.
PloS one 20150713 7
[This corrects the article DOI: 10.1371/journal.pone.0119954.]. ...[more]
Similar Datasets
Project description:Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins. Moreover, it decreased the activity of RhoA, but increased the expression of Rac1. In addition, PRPF triggered the epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116, PC3 human prostate, and B16-F10 melanoma cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRPF. Taken together, these results indicate that PRPF blocks the apoptotic effects of resveratrol by activating cell survival signaling pathways, rearranging the actin cytoskeleton, and inducing EMT. The elucidation of the mechanisms that underlie anticancer drug resistance and the anti-apoptosis effect of PRPF may provide a therapeutic basis for inhibiting tumor growth and preventing metastasis in various cancers.
| S-EPMC5593591 | biostudies-literature
Project description:Over a century of scientific inquiry since the discovery of v-SRC but still no final judgement on SRC function. However, a significant body of work has defined Src family kinases as key players in tumor progression, invasion and metastasis in human cancer. With the ever-growing evidence supporting the role of epithelial-mesenchymal transition (EMT) in invasion and metastasis, so does our understanding of the role SFKs play in mediating these processes. Here we describe some key mechanisms through which Src family kinases play critical role in epithelial homeostasis and how their function is essential for the propagation of invasive signals. Video abstract.
| S-EPMC8247114 | biostudies-literature
Project description:Epithelial ovarian cancer cells enhance their ability to migrate and invade through the epithelial-mesenchymal transition (EMT), resulting in cell seeding and metastasis in the peritoneal cavity and onto adjacent organ surfaces. It has been speculated that cytoskeletal dynamics, such as those of the actin filament, play a role in enhanced cell motility; however, direct evidence has not been provided. Herein, we have directly measured pico- to nanonewton-scale mechanical forces generated by actin dynamics of ovarian cancer SKOV-3 cells upon binding of integrin α5β1 to fibronectin (FN), i.e., formation of a focal adhesion, using real-time atomic force microscopy (AFM) in a force spectroscopy mode. The dendrimer surface chemistry through which FN was immobilized on the AFM probe surfaces further enhanced the sensitivity of the force measurement by 1.5-fold. Post-EMT SKOV-3 cells, induced by transforming growth factor-β, generated larger focal adhesion mechanical forces (17 and 41 nN before and after EMT, respectively) with migration faster than that of pre-EMT cells. Importantly, 22% of the forces transmitted through a single FN-integrin α5β1 pair from post-EMT cells were shown to be sufficient to rupture the binding between FN and integrin α5β1 on the cells, a result which is not observed on pre-EMT cells. This implies that post-EMT cells, by generating forces strong enough to break the FN-integrin binding, migrate and metastasize beyond the ovary, whereas pre-EMT cancer cells are confined in the ovary without such force generation. These results demonstrate quantitative and direct evidence for the role of actin dynamics in the enhanced motility of post-EMT ovarian cancer cells, providing a fundamental insight into the mechanism of ovarian cancer metastasis.
| S-EPMC3784653 | biostudies-literature
Project description:In triple-negative breast cancer (TNBC), the high recurrence rate, increased invasion and aggressive metastatic formation dictate patient survival. We previously demonstrated a critical role for the Na+/H+ exchanger isoform 1 (NHE1) in controlling metastasis of triple-negative cells. Here, we investigated the effect of changes to three regulatory loci of NHE1. Two via the Ras/Raf/ERK/p90RSK pathway: p90RSK/14-3-3 (S703A) and ERK1/2 (S766,770,771A, SSSA) and a third via a calmodulin-binding domain (K641,R643,645,647E, 1K3R4E). MDA-MB-231 cells with a mutation at the p90RSK site (S703A-NHE1) changed from a wild-type mesenchymal morphology to a smaller epithelial-like phenotype with a loss of expression of mesenchymal marker vimentin. S703A cells also had reduced metastatic potential and markedly decreased rates of migration, invasion, spheroid growth, anchorage-dependent and soft agar colony formation. Similarly, BI-D1870, a specific inhibitor of p90RSK, significantly inhibited the metastatic potential of highly invasive MDA-MB-231 and moderately invasive MDA-MB-468 TNBC cells, but was minimally effective in non-invasive Hs578T TNBC cells. In contrast, invasion and spheroid growth were unaffected in cells containing NHE1 with mutations interfering with its activation by ERK1/2 (SSSA), though rates of migration and colony formation were reduced. Cells with a constitutive activation of NHE1 via the 1K3R4E mutation exhibited higher rates of migration, invasion, and spheroid growth. Taken together, our data demonstrate the critical role of NHE1 in metastasis, and suggest a novel link between NHE1 and the expression and cytosolic organization of vimentin, a key factor in epithelial-mesenchymal transition, that is dependent on p90RSK/14-3-3-mediated activation of the exchanger.
| S-EPMC5008271 | biostudies-literature
Project description:Metastasis is the end stage of cancer progression and the direct cause of most cancer-related deaths. The spreading of cancer cells from the primary site to distant organs is a multistep process known as the metastatic cascade, including local invasion, intravasation, survival in the circulation, extravasation, and colonization. Each of these steps is driven by the acquisition of genetic and/or epigenetic alterations within cancer cells, leading to subsequent transformation of metastatic cells. Epithelial-mesenchymal transition (EMT), a cellular process mediating the conversion of cell from epithelial to mesenchymal phenotype, and its reverse transformation, termed mesenchymal-epithelial transition (MET), together endow metastatic cells with traits needed to generate overt metastases in different scenarios. The dynamic shift between these two phenotypes and their transitional state, termed partial EMT, emphasizes the plasticity of EMT. Recent advances attributed this plasticity to epigenetic regulation, which has implications for the therapeutic targeting of cancer metastasis. In this review, we will discuss the association between epigenetic events and the multifaceted nature of EMT, which may provide insights into the steps of the cancer metastatic cascade.
| S-EPMC8117142 | biostudies-literature
Project description:Prostate cancer (PCa) is one of the most common cancers in men. Metastasis is the leading cause of death in prostate cancer patients. One of the crucial processes involved in metastatic spread is the "epithelial-mesenchymal transition" (EMT), which allows cells to acquire the ability to invade distant organs. Liver X Receptors (LXRs) are nuclear receptors that have been demonstrated to regulate EMT in various cancers, including hepatic cancer. Our study reveals that the LXR pathway can control pro-invasive cell capacities through EMT in prostate cancer, employing ex vivo and in vivo approaches. We characterized the EMT status of the commonly used LNCaP, DU145, and PC3 prostate cancer cell lines through molecular and immunohistochemistry experiments. The impact of LXR activation on EMT function was also assessed by analyzing the migration and invasion of these cell lines in the absence or presence of an LXR agonist. Using in vivo experiments involving NSG-immunodeficient mice xenografted with PC3-GFP cells, we were able to study metastatic spread and the effect of LXRs on this process. LXR activation led to an increase in the accumulation of Vimentin and Amphiregulin in PC3. Furthermore, the migration of PC3 cells significantly increased in the presence of the LXR agonist, correlating with an upregulation of EMT. Interestingly, LXR activation significantly increased metastatic spread in an NSG mouse model. Overall, this work identifies a promoting effect of LXRs on EMT in the PC3 model of advanced prostate cancer.
| S-EPMC11353074 | biostudies-literature
Project description: Not available
| S-EPMC9596398 | biostudies-literature
Project description:Epithelial-mesenchymal transition (EMT) plays an important role in development and also in initiation of metastasis during cancer. Disruption of cell-cell contacts during EMT allowing cells to detach from and migrate away from their neighbors remains poorly understood. Using immunofluorescent staining and live-cell imaging, we analyzed early events during EMT induced by epidermal growth factor (EGF) in IAR-20 normal epithelial cells. Control cells demonstrated stable adherens junctions (AJs) and robust contact paralysis, whereas addition of EGF caused rapid dynamic changes at the cell-cell boundaries: fragmentation of the circumferential actin bundle, assembly of actin network in lamellipodia, and retrograde flow. Simultaneously, an actin-binding protein EPLIN was phosphorylated, which may have decreased the stability of the circumferential actin bundle. Addition of EGF caused gradual replacement of linear E-cadherin-based AJs with dynamic and unstable punctate AJs, which, unlike linear AJs, colocalized with the mechanosensitive protein zyxin, confirming generation of centripetal force at the sites of cell-cell contacts during EMT. Our data show that early EMT promotes heightened dynamics at the cell-cell boundaries-replacement of stable AJs and actin structures with dynamic ones-which results in overall weakening of cell-cell adhesion, thus priming the cells for front-rear polarization and eventual migration.
| S-EPMC7140442 | biostudies-literature
Project description:The epithelial-mesenchymal transition (EMT) is a developmental program co-opted by tumor cells that aids the initiation of the metastatic cascade. Tumor cells that undergo EMT are relatively chemoresistant, and there are currently no therapeutic avenues specifically targeting cells that have acquired mesenchymal traits. We show that treatment of mesenchymal-like triple-negative breast cancer (TNBC) cells with the microtubule-destabilizing chemotherapeutic eribulin, which is FDA-approved for the treatment of advanced breast cancer, leads to a mesenchymal-epithelial transition (MET). This MET is accompanied by loss of metastatic propensity and sensitization to subsequent treatment with other FDA-approved chemotherapeutics. We uncover a novel epigenetic mechanism of action that supports eribulin pretreatment as a path to MET induction that curtails metastatic progression and the evolution of therapy resistance.
| S-EPMC10153261 | biostudies-literature
Project description:Cancer stem cells (CSCs) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem-like cells (CSLCs) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLCs. Sphere cancer stem-like cells were induced from a human hepatoma cell line (SK-HEP-1) in a unique medium containing neural survival factor-1. Splenic injection of cells into immune-deficient mice was used to assess hematogenous liver metastasis. Transcriptomic strand-specific RNA-sequencing analysis, quantitative real-time PCR, and flow cytometry were carried out to examine the expression of epithelial-mesenchymal transition (EMT)-related genes. Splenic injection of CSLCs resulted in a significantly increased frequency of liver metastasis compared to parental cancer cells (P < .05). In CSLCs, a mesenchymal marker, Vimentin, and EMT-promoting transcription factors, Snail and Twist1, were upregulated compared to parental cells. Correspondingly, significant enrichment of the molecular signature of the EMT in CSLCs relative to parental cancer cells was shown (q < 0.01) by RNA-sequencing analysis. This analysis also revealed differential expression of CD44 isoforms between CSLCs and parental cancer cells. Increasing CD44 isoforms containing an extra exon were observed, and the standard CD44 isoform decreased in CSLCs compared to parental cells. Interestingly, another CD44 variant isoform encoding a short cytoplasmic tail was also upregulated in CSLCs (11.7-fold). Our induced CSLCs possess an increased liver metastatic potential in which promotion of the EMT and upregulation of CD44 variant isoforms, especially short-tail, were observed.
| S-EPMC5891178 | biostudies-literature