Actin cytoskeletal control during epithelial to mesenchymal transition: focus on the pancreas and intestinal tract

Morris, Hayley; Machesky, Laura M.

doi:10.1038/bjc.2014.658

Cited by 61 publications

(48 citation statements)

References 48 publications

(60 reference statements)

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“…The migratory ability is related to actin cytoskeleton that maintains the polarity of cells, which is essential for normal tissue homeostasis and, when disrupted, can lead to tumor promotion (Morris & Machesky, 2015; Yilmaz & Christofori, 2010). Moreover, the actin bundles destructuration is correlated with a mechanistic pathway that drives uncontrolled growth and cancer progression (Katira et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Lucchetti

Perelli

Colella

et al. 2020

Journal Cellular Physiology

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Ultrasound (US) offers potentially important opportunities from a therapeutic point of view. Thus, the study of the biological effects of US on cancer cells is important to understand the consequences of these changes on the malignant phenotype. This study aimed to investigate the effects of low‐intensity ultrasound (LIPUS) on the phenotype of colorectal cancer cell lines. Cell proliferation was evaluated by viability test and by evaluation of pERK expression, while cell motility using the scratch test. Cell differentiation was evaluated assessing alkaline phosphatase activity. Epithelial mesenchymal transition was assessed by analyzing the expression of Vimentin and E‐Cadherin. Release and uptake of extracellular vesicles (EVs) were evaluated by flow cytometry. LIPUS effects on the organization of cytoskeleton were analyzed by confocal microscopy and by evaluation of Rho GTPase expression. No alterations in vitality and clonogenicity were observed when the intermediate (0.4 MPa) and the lowest (0.035 MPa) acoustic intensities were administered while the treatment with high intensity (1 MPa) induced a reduction of both cell viability and clonogenicity in both cell lines in a frequency‐dependent manner. LIPUS promoted the differentiation of colon cancer cells, affected epithelial‐to‐mesenchymal transition, promoted the closure of a wound as well as increased the release of EVs compared with untreated cells. LIPUS‐induced increase in cell motility was likely due to a Rho GTPase‐dependent mechanism. Overall, the results obtained warrant further studies on the potential combined effect of LIPUS with differentiating agents and on their potential use in a clinical setting.

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Section: Discussionmentioning

confidence: 99%

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Lucchetti

Perelli

Colella

et al. 2020

Journal Cellular Physiology

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“…It is also involved in cell signaling transduction, thus controlling a variety of cellular responses. [3][4][5] ECM stiffness has been shown to induce actin cytoskeletal reorganization and contractility, thereby controlling adhesion, migration, cell cycle progression, and differentiation. [6][7][8] The translation of ECM stiffness into intracellular signals to change cell behavior is mainly mediated by transmembrane receptors, known as integrins.…”

Section: Molecular Regulation By Mechanical Stimulationmentioning

confidence: 99%

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

et al. 2015

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ABSTRACT. Tissue development is orchestrated by the coordinated activities of both chemical and physical regulators. While much attention has been given to the role that chemical regulators play in driving development, researchers have recently begun to elucidate the important role that the mechanical properties of the extracellular environment play. For instance, the stiffness of the extracellular environment has a role in orienting cell division, maintaining tissue boundaries, directing cell migration, and driving differentiation. In addition, extracellular matrix stiffness is important for maintaining normal tissue homeostasis, and when matrix mechanics become imbalanced, disease progression may ensue. In this article, we will review the important role that matrix stiffness plays in dictating cell behavior during development, tissue homeostasis, and disease progression.

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“…Although the perturbation of epithelial cell–cell junctions is a main trait of EMT in PDAC, 4 PDAC with metastatic traits do not lose of E-cadherin, suggesting that EMT-related markers are not prognostic markers 5 . Cytoskeletal reorganization, 6 extracellular matrix (ECM) remodeling, and matrix metalloproteinase (MMPs) 7 contribute to PDAC aggressiveness in cooperation with soluble growth factor or cytokines, with TGF-β1 as a crucial player 8 . Alternative splicing is known to play a prominent role in tumor progression and the derived isoforms may represent powerful diagnostic and prognostic factors, 9 as we have recently shown for hMENA alternative splicing in early stage non-small cell lung cancer (NSCLC) 10 .…”

Section: Introductionmentioning

confidence: 99%

The pattern of hMENA isoforms is regulated by TGF-β1 in pancreatic cancer and may predict patient outcome

Melchionna¹,

Iapicca²,

Modugno³

et al. 2016

OncoImmunology

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease in need of prognostic markers to address therapeutic choices. We have previously shown that alternative splicing of the actin regulator, hMENA, generates hMENA11a, and hMENAΔv6 isoforms with opposite roles in cell invasion. We examined the expression pattern of hMENA isoforms by immunohistochemistry, using anti-pan hMENA and specific anti-hMENA11a antibodies, in 285 PDACs, 15 PanINs, 10 pancreatitis, and normal pancreas. Pan hMENA immunostaining, absent in normal pancreas and low-grade PanINs, was weak in PanIN-3 and had higher levels in virtually all PDACs with 64% of cases showing strong staining. Conversely, the anti-invasive hMENA11a isoform only showed strong staining in 26% of PDAC. The absence of hMENA11a in a subset (34%) of pan-hMENA-positive tumors significantly correlated with poor outcome. The functional effects of hMENA isoforms were analyzed by loss and gain of function experiments in TGF-β1-treated PDAC cell lines. hMENA11a knock-down in PDAC cell lines affected cell–cell adhesion but not invasion. TGF-β1 cooperated with β-catenin signaling to upregulate hMENA and hMENAΔv6 expression but not hMENA11a In the absence of hMENA11a, the hMENA/hMENAΔv6 up-regulation is crucial for SMAD2-mediated TGF-β1 signaling and TGF-β1-induced EMT. Since the hMENA isoform expression pattern correlates with patient outcome, the data suggest that hMENA splicing and related pathways are novel key players in pancreatic tumor microenvironment and may represent promising targets for the development of new prognostic and therapeutic tools in PDAC.

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Actin cytoskeletal control during epithelial to mesenchymal transition: focus on the pancreas and intestinal tract

Cited by 61 publications

References 48 publications

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

The pattern of hMENA isoforms is regulated by TGF-β1 in pancreatic cancer and may predict patient outcome

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