scholarly journals Fascin1 empowers YAP mechanotransduction and promotes cholangiocarcinoma development

2020 ◽  
Author(s):  
Arianna Pocaterra ◽  
Cindy Ament ◽  
Silvia Ribback ◽  
Xin Chen ◽  
Matthias Evert ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Mouse Liver ◽  
Control Cell ◽  
Cell Behavior ◽  
Mechanical Forces ◽  
Poor Patient ◽  
Key Factor ◽  
Patient Prognosis ◽  
Intrahepatic Cholangiocarcinomas

AbstractMechanical forces control cell behavior, including cancer progression. Cells sense forces through actomyosin and YAP, but what regulators of actin mechanotransduction play relevant roles in vivo remains unclear. Here we identify the Fascin1 F-actin bundling protein as a key factor sustaining YAP activation in response to ECM mechanical cues. This is relevant in the mouse liver, where Fascin1 regulates YAP-dependent hepatocyte dedifferentiation. Moreover, Fascin1 is required in the AKT/NICD system and sufficient together with AKT to induce cholangiocarcinomas in mice, recapitulating genetic YAP requirements, and its expression in intrahepatic cholangiocarcinomas correlates with aggressiveness and poor patient prognosis. We propose that Fascin1 represents a pro-oncogenic mechanism that can be exploited during intrahepatic cholangiocarcinoma development to overcome a mechanical tumor-suppressive environment.

scholarly journals Fascin1 empowers YAP mechanotransduction and promotes cholangiocarcinoma development

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Arianna Pocaterra ◽  
Gloria Scattolin ◽  
Patrizia Romani ◽  
Cindy Ament ◽  
Silvia Ribback ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Control Cell ◽  
Actin Dynamics ◽  
Cell Behavior ◽  
Mechanical Forces ◽  
Poor Patient ◽  
Cholangiocarcinoma Cell ◽  
Patient Prognosis

AbstractMechanical forces control cell behavior, including cancer progression. Cells sense forces through actomyosin to activate YAP. However, the regulators of F-actin dynamics playing relevant roles during mechanostransduction in vitro and in vivo remain poorly characterized. Here we identify the Fascin1 F-actin bundling protein as a factor that sustains YAP activation in response to ECM mechanical cues. This is conserved in the mouse liver, where Fascin1 regulates YAP-dependent phenotypes, and in human cholangiocarcinoma cell lines. Moreover, this is relevant for liver tumorigenesis, because Fascin1 is required in the AKT/NICD cholangiocarcinogenesis model and it is sufficient, together with AKT, to induce cholangiocellular lesions in mice, recapitulating genetic YAP requirements. In support of these findings, Fascin1 expression in human intrahepatic cholangiocarcinomas strongly correlates with poor patient prognosis. We propose that Fascin1 represents a pro-oncogenic mechanism that can be exploited during intrahepatic cholangiocarcinoma development to overcome a mechanical tumor-suppressive environment.

scholarly journals Matrix nanotopography as a regulator of cell function

2012 ◽  
Vol 197 (3) ◽  
pp. 351-360 ◽  
Author(s):  
Deok-Ho Kim ◽  
Paolo P. Provenzano ◽  
Chris L. Smith ◽  
Andre Levchenko
Keyword(s):  
Signal Transduction ◽  
Cell Function ◽  
Control Cell ◽  
Signal Transduction Pathways ◽  
Cell Behavior ◽  
Powerful Means ◽  
Cell Processes ◽  
Chemical Factors ◽  
Physical Interactions

The architecture of the extracellular matrix (ECM) directs cell behavior by providing spatial and mechanical cues to which cells respond. In addition to soluble chemical factors, physical interactions between the cell and ECM regulate primary cell processes, including differentiation, migration, and proliferation. Advances in microtechnology and, more recently, nanotechnology provide a powerful means to study the influence of the ECM on cell behavior. By recapitulating local architectures that cells encounter in vivo, we can elucidate and dissect the fundamental signal transduction pathways that control cell behavior in critical developmental, physiological, and pathological processes.

scholarly journals CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies

2016 ◽  
Vol 40 (3-4) ◽  
pp. 567-578 ◽  
Author(s):  
Min Fang ◽  
Junrong Wu ◽  
Xin Lai ◽  
Huaying Ai ◽  
Yifeng Tao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Histological Grade ◽  
Prognostic Significance ◽  
Lymphatic Invasion ◽  
Poor Patient ◽  
Patient Prognosis ◽  
Gastric Cancer Progression ◽  
Prognostic Power ◽  
Cd44v6 Expression

Background/Aims: The prognostic power of the levels of total CD44 and its isoform CD44v6 for patients with gastric cancer (GC) remains controversial. Therefore, our study aims to generalize the clinicopathological and prognostic significance of these two proteins in GC. Methods: A literature search of the PubMed, Web of Science and Embase databases was conducted to identify eligible studies. The odds ratio (OR) with a 95% confidence interval (CI) was used to assess the effects. Results: In all, 42 studies including 6,229 patients were included in this analysis. Total CD44 was mentioned in 21 papers, and the results showed that CD44 was positively correlated with the T category, the N category, distant metastasis, lymphatic invasion and TNM stage. Moreover, patients with CD44 overexpression had a lower 5-year overall survival (OS) rate (OR = 3.35, 95%CI = 1.83-6.13). CD44v6 was mentioned in 24 studies, with results that were similar to those for total CD44. However, total CD44 or CD44v6 expression was not correlated with tumor size and histological grade. Conclusion: High CD44 or CD44v6 expression levels were correlated with cancer progression and poor prognosis in patients with GC. Both CD44 and CD44v6 may be useful diagnostic or prognostic biomarkers for GC.

scholarly journals Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Francisca Benavente ◽  
Katja M Piltti ◽  
Mitra J Hooshmand ◽  
Aileen A Nava ◽  
Anita Lakatos ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Control Cell ◽  
Screening Strategy ◽  
Receptor Expression ◽  
Therapeutic Window ◽  
Cell Behavior ◽  
Human Neural Stem Cells ◽  
Cord Injury

C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet been identified. Here, we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior. Using an unbiased screening strategy, we identified five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, c-MET, and ADCY5). We further investigated the interaction between C1q and CD44 , demonstrating that CD44 mediates C1q induced hNSC signaling and chemotaxis in vitro, and hNSC migration and functional repair in vivo after spinal cord injury. These results reveal a receptor-mediated mechanism for C1q modulation of NSC behavior and show that modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.

scholarly journals GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 19
Author(s):  
Hye-Mi Ahn ◽  
Eun-Young Choi ◽  
Youn-Jae Kim
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
The Public ◽  
Adenocarcinoma Cells ◽  
No Signaling ◽  
Tcga Dataset ◽  
Patient Prognosis

Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma TCGA dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma.

scholarly journals TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

2014 ◽  
Vol 112 (1) ◽  
pp. 226-231 ◽  
Author(s):  
Ivano Amelio ◽  
Satoshi Inoue ◽  
Elke K. Markert ◽  
Arnold J. Levine ◽  
Richard A. Knight ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Human Lung Cancer ◽  
Regulatory Subunit ◽  
Independent Manner ◽  
Induced Tumors ◽  
Patient Prognosis

Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activation are associated with cancer progression. Here, we demonstrate that the transcription factor TAp73 opposes HIF-1 activity through a nontranscriptional mechanism, thus affecting tumor angiogenesis. TAp73-deficient mice have an increased incidence of spontaneous and chemically induced tumors that also display enhanced vascularization. Mechanistically, TAp73 interacts with the regulatory subunit (α) of HIF-1 and recruits mouse double minute 2 homolog into the protein complex, thus promoting HIF-1α polyubiquitination and consequent proteasomal degradation in an oxygen-independent manner. In human lung cancer datasets, TAp73 strongly predicts good patient prognosis, and its expression is associated with low HIF-1 activation and angiogenesis. Our findings, supported by in vivo and clinical evidence, demonstrate a mechanism for oxygen-independent HIF-1 regulation, which has important implications for individualizing therapies in patients with cancer.

scholarly journals Recent advance in surface modification for regulating cell adhesion and behaviors

2020 ◽  
Vol 9 (1) ◽  
pp. 971-989
Author(s):  
Shuxiang Cai ◽  
Chuanxiang Wu ◽  
Wenguang Yang ◽  
Wenfeng Liang ◽  
Haibo Yu ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Adhesion ◽  
Control Cell ◽  
Biochemical Properties ◽  
Cell Behavior ◽  
Factors Affecting ◽  
Artificial Surfaces ◽  
The Matrix

AbstractCell adhesion is a basic requirement for anchorage-dependent cells to survive on the matrix. It is the first step in a series of cell activities, such as cell diffusion, migration, proliferation, and differentiation. In vivo, cells are surrounded by extracellular matrix (ECM), whose physical and biochemical properties and micromorphology may affect and regulate the function and behavior of cells, causing cell reactions. Cell adhesion is also the basis of communication between cells and the external environment and plays an important role in tissue development. Therefore, the significance of studying cell adhesion in vitro has become increasingly prominent. For instance, in the field of tissue engineering and regenerative medicine, researchers have used artificial surfaces of different materials to simulate the properties of natural ECM, aiming to regulate the behavior of cell adhesion. Understanding the factors that affect cell behavior and how to control cell behavior, including cell adhesion, orientation, migration, and differentiation on artificial surfaces, is essential for materials and life sciences, such as advanced biomedical engineering and tissue engineering. This article reviews various factors affecting cell adhesion as well as the methods and materials often used in investigating cell adhesion.

scholarly journals B7-H3 Promotes Prostate Cancer Progression in Mice by Antagonizing Myeloid-Derived Suppressor Cell Apoptosis

2020 ◽  
Vol 19 ◽  
pp. 153303382097164
Author(s):  
Yunfen Zhou ◽  
Guangbo Zhang ◽  
Weijie Zhang ◽  
Xuedong Wei ◽  
Jianquan Hou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Control Cell ◽  
Cancer Cell Line ◽  
Cancer Prognosis ◽  
Prostate Cancer Progression

Background: B7-H3 is an important immunomodulatory molecule, and clinical studies have confirmed that its expression level is closely correlated with prostate cancer prognosis. However, the mechanism of its biological action is unclear. Methods: An engineered cell line overexpressing B7-H3 was constructed. Cell apoptosis, growth and proliferation assays in vitro and an animal model in vivo were performed to analyze the role and possible mechanism of B7-H3 in promoting prostate cancer progression. Results: Compared with the control cell line (Mock-RM-1), the B7-H3-overexpressing prostate cancer cell line (B7-H3-RM-1) showed no significant growth differences in vitro, whereas the in vivo tumorigenesis rate of B7-H3-RM-1 was significantly higher than that of Mock-RM-1. These results suggest that B7-H3indirectly, rather than directly, promotes prostate cancer progression. Further analysis revealed that significantly higher levels of myeloid-derived suppressor cells (MDSCs) accumulated in vivo in B7-H3-RM-1 tumor-bearing mice than in Mock-RM-1 mice. In vitro and in vivo experiments showed that B7-H3-RM-1 cells significantly antagonized MDSC apoptosis. To further confirm the role of MDSCs in B7-H3-mediated prostate cancer progression, model mice were pretreated with cyclophosphamide before inoculation to clear immune cells and achieve myelo suppression. The results showed no significant differences in tumor growth between the B7-H3-RM-1 group and the Mock-RM-1 group. Conclusions: We found, for the first time, that B7-H3 can antagonize MDSC apoptosis, leading to MDSC accumulation in the tumor microenvironment and thereby promoting prostate cancer progression.

scholarly journals The “NF-ĸB interacting long noncoding RNA” (NKILA) transcript is antisense to cancer-associated gene PMEPA1

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 96 ◽  
Author(s):  
Johannes M. Dijkstra ◽  
David B. Alexander
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Binding Motif ◽  
Breast Cancers ◽  
Correct Interpretation ◽  
Poor Patient ◽  
Direct Binding ◽  
Immune Pathways ◽  
Patient Prognosis

This correspondence concerns a recent publication inCancer Cellby Liu et al.1 who analyzed a long noncoding RNA (lncRNA) that they designated “NKILA”. Liu et al. found thatNKILA(1) is upregulated by immunostimulants, (2) has a promoter with an NF-ĸB binding motif, (3) can bind to the p65 protein of the NF-ĸB transcription factor and then interfere with phosphorylation of IĸBα, and (4) negatively affects functions that involve NF-ĸB pathways.  And, importantly, they found that (5) lowNKILAexpression in breast cancers is associated with poor patient prognosis.  However, they entirely failed to mentionPMEPA1, a gene which runs antisense toNKILA, and the expression of which is associated with several tumors and which encodes a protein that participates in immune pathways.ThePMEPA1locus, including its promoter region, which Liu et al.1only discuss in regard toNKILA, is highly conserved through evolution.  Our impression is thatNKILAemerged only later in evolution, possibly as an additional means ofPMEPA1regulation.  Liu et al., however, only consider direct binding betweenNKILAand NF-ĸB as the mechanism for theirin vivoobservations ofNKILAfunction, but do not provide solid evidence for their model.  Ifin vivoobservations by Liu et al. could be explained byNKILAregulation ofPMEPA1, it would contribute to the establishment ofPMEPA1as an important topic of cancer research.  We feel that the herein presented discussion is necessary for a correct interpretation of the Liu et al. article.

scholarly journals Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo

2014 ◽  
Vol 25 (24) ◽  
pp. 3835-3850 ◽  
Author(s):  
Michael Levin
Keyword(s):  
Gap Junctions ◽  
Control Cell ◽  
Limb Regeneration ◽  
Cell Types ◽  
Resting Potential ◽  
Whole Body ◽  
Transcriptional Networks ◽  
Cell Behavior ◽  
Potential Control

In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering.

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