scholarly journals p120 catenin is essential for mesenchymal cadherin–mediated regulation of cell motility and invasiveness

2006 ◽  
Vol 174 (7) ◽  
pp. 1087-1096 ◽  
Author(s):  
Masahiro Yanagisawa ◽  
Panos Z. Anastasiadis
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Tumor Progression ◽  
Cellular Phenotype ◽  
Epithelial Tumor ◽  
P120 Catenin ◽  
Rhoa Activity ◽  
Inappropriate Expression ◽  
E Cadherin

During epithelial tumor progression, the loss of E-cadherin expression and inappropriate expression of mesenchymal cadherins coincide with increased invasiveness. Reexpression experiments have established E-cadherin as an invasion suppressor. However, the mechanism by which E-cadherin suppresses invasiveness and the role of mesenchymal cadherins are poorly understood. We show that both p120 catenin and mesenchymal cadherins are required for the invasiveness of E-cadherin–deficient cells. p120 binding promotes the up-regulation of mesenchymal cadherins and the activation of Rac1, which are essential for cell migration and invasiveness. p120 also promotes invasiveness by inhibiting RhoA activity, independently of cadherin association. Furthermore, association of endogenous p120 with E-cadherin is required for E-cadherin–mediated suppression of invasiveness and is accompanied by a reduction in mesenchymal cadherin levels. The data indicate that p120 acts as a rheostat, promoting a sessile cellular phenotype when associated with E-cadherin or a motile phenotype when associated with mesenchymal cadherins.

scholarly journals Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria De Luca ◽  
Roberta Romano ◽  
Cecilia Bucci
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Downstream Signaling ◽  
Late Endosomes ◽  
Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

scholarly journals Role of the Polarity Determinant Crumbs in Suppressing Mammalian Epithelial Tumor Progression

2008 ◽  
Vol 68 (11) ◽  
pp. 4105-4115 ◽  
Author(s):  
Cristina M. Karp ◽  
Ting Ting Tan ◽  
Robin Mathew ◽  
Deidre Nelson ◽  
Chandreyee Mukherjee ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Epithelial Tumor

The role of E-cadherin and scatter factor in tumor invasion and cell motility

1991 ◽  
pp. 109-126 ◽  
Author(s):  
Jürgen Behrens ◽  
K. Michael Weidner ◽  
Uwe H. Frixen ◽  
Jörg H. Schipper ◽  
Martin Sachs ◽  
...  
Keyword(s):  
Cell Motility ◽  
Tumor Invasion ◽  
Scatter Factor ◽  
E Cadherin

scholarly journals Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1264
Author(s):  
Yuxing Huang ◽  
Xin Yi ◽  
Chenlu Kang ◽  
Congying Wu
Keyword(s):  
Signal Transduction ◽  
Cell Motility ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Protein Abundance ◽  
Rhoa Activity ◽  
Cytoskeletal Dynamics ◽  
Active Pool ◽  
Spatiotemporal Control

Small GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components’ feedback to upstream signaling factors remains largely elusive. Here, we report an intriguing finding that disruption of the Arp2/3-branched actin specifically reduces RhoA activity but upregulates its total protein abundance. We further dissect the mechanisms underlying these circumstances and identify the altered cortactin/p190RhoGAP interaction and weakened CCM2/Smurf1 binding to be involved in GTP-RhoA reduction and total RhoA increase, respectively. Moreover, we find that cytokinesis defects induced by Arp2/3 inhibition can be rescued by activating RhoA. Our study reveals an intricate feedback from the actin cytoskeleton to the small GTPase. Our work highlights the role of Arp2/3-branched actin in signal transduction aside from its function in serving as critical cytoskeletal components to maintain cell morphology and motility.

scholarly journals Hyaluronan–CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9

2002 ◽  
Vol 158 (6) ◽  
pp. 1133-1144 ◽  
Author(s):  
Paola Spessotto ◽  
Francesca Maria Rossi ◽  
Massimo Degan ◽  
Raffaele Di Francia ◽  
Roberto Perris ◽  
...  
Keyword(s):  
Cell Migration ◽  
Bone Resorption ◽  
Cell Motility ◽  
Binding Affinity ◽  
Antisense Oligonucleotides ◽  
Substrate Binding ◽  
Down Regulation ◽  
Multinucleated Cells ◽  
Cell Substrate

Osteoclast (OC) precursors migrate to putative sites of bone resorption to form functionally active, multinucleated cells. The preOC FLG 29.1 cells, known to be capable of irreversibly differentiating into multinucleated OC-like cells, displayed several features of primary OCs, including expression of specific integrins and the hyaluronan (HA) receptor CD44. OC-like FLG 29.1 cells adhered to and extensively migrated through membranes coated with fibronectin, vitronectin, and laminins, but, although strongly binding to HA, totally failed to move on this substrate. Moreover, soluble HA strongly inhibited OC-like FLG 29.1 cell migration on the permissive matrix substrates, and this behavior was dependent on its engagement with CD44, as it was fully restored by function-blocking anti-CD44 antibodies. HA did not modulate the cell–substrate binding affinity/avidity nor the expression levels of the corresponding integrins. MMP-9 was the major secreted metalloproteinase used by OC-like FLG 29.1 cells for migration, because this process was strongly inhibited by both TIMP-1 and GM6001, as well as by MMP-9–specific antisense oligonucleotides. After HA binding to CD44, a strong down-regulation of MMP-9 mRNA and protein was detected. These findings highlight a novel role of the HA–CD44 interaction in the context of OC-like cell motility, suggesting that it may act as a stop signal for bone-resorbing cells.

scholarly journals The comprehensive role of E-cadherin in maintaining prostatic epithelial integrity during oncogenic transformation and tumor progression

PLoS Genetics ◽  
2019 ◽  
Vol 15 (10) ◽  
pp. e1008451 ◽  
Author(s):  
Adam Olson ◽  
Vien Le ◽  
Joseph Aldahl ◽  
Eun-Jeong Yu ◽  
Erika Hooker ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Oncogenic Transformation ◽  
Epithelial Integrity ◽  
E Cadherin

scholarly journals Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽  
2015 ◽  
Vol 35 (24) ◽  
pp. 3151-3162 ◽  
Author(s):  
Q Zhang ◽  
T Wei ◽  
K Shim ◽  
K Wright ◽  
K Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

scholarly journals E-Cadherin/p120-Catenin and Tetraspanin Co-029 Cooperate for Cell Motility Control in Human Colon Carcinoma

2010 ◽  
Vol 70 (19) ◽  
pp. 7674-7683 ◽  
Author(s):  
Céline Greco ◽  
Marie-Pierre Bralet ◽  
Naouel Ailane ◽  
Anne Dubart-Kupperschmitt ◽  
Eric Rubinstein ◽  
...  
Keyword(s):  
Cell Motility ◽  
Colon Carcinoma ◽  
Human Colon ◽  
P120 Catenin ◽  
Human Colon Carcinoma ◽  
E Cadherin
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