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Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition

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Martín-Villar, Ester, Megías, Diego, Castel, Susanna, Yurrita, Maria Marta, Vilaró, Senén, Quintanilla, Miguel·2006·Journal of Cell Science

DOI 10.1242/jcs.03218

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Abstract

Podoplanin is a small membrane mucin expressed in tumors associated with malignant progression. It is enriched at cell-surface protrusions where it colocalizes with members of the ERM (ezrin, radixin, moesin) protein family. Here, we found that human podoplanin directly interacts with ezrin (and moesin) in vitro and in vivo through a cluster of basic amino acids within its cytoplasmic tail, mainly through a juxtamembrane dipeptide RK. Podoplanin induced an epithelial-mesenchymal transition in MDCK cells linked to the activation of RhoA and increased cell migration and invasiveness. Fluorescence time-lapse video observations in migrating cells indicate that podoplanin might be involved in ruffling activity as well as in retractive processes. By using mutant podoplanin constructs fused to green fluorescent protein we show that association of the cytoplasmic tail with ERM proteins is required for upregulation of RhoA activity and epithelial-mesenchymal transition. Furthermore, expression of either a dominant-negative truncated variant of ezrin or a dominant-negative mutant form of RhoA blocked podoplanin-induced RhoA activation and epithelial-mesenchymal transition. These results provide a mechanistic basis to understand the role of podoplanin in cell migration or invasiveness.

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Cano, A., Pérez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., Portillo, F., & Nieto, M. A. (2000) · Nature Cell Biology · doi:10.1038/35000025 · Cited by 3,668
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Batlle, E., Sancho, E., Francí, C., Domínguez, D., Monfar, M., Baulida, J., & García de Herreros, A. (2000) · Nature Cell Biology · doi:10.1038/35000034 · Cited by 2,666
Putting tumours in context
Bissell, M. J., & Radisky, D. (2001) · Nature Reviews Cancer · doi:10.1038/35094059 · Cited by 2,180
ERM proteins and merlin: integrators at the cell cortex
Bretscher, A., Edwards, K., & Fehon, R. G. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm882 · Cited by 1,306
RHO-GTPases and cancer
Sahai, E., & Marshall, C. J. (2002) · Nature Reviews Cancer · doi:10.1038/nrc725 · Cited by 1,261
Rho GTPases and cell migration
Ridley, A. J. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.15.2713 · Cited by 1,191
The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors
Bolós, V., Peinado, H., Pérez-Moreno, M. A., Fraga, M. F., Esteller, M., & Cano, A. (2003) · Journal of Cell Science · doi:10.1242/jcs.00224 · Cited by 1,100
Angiosarcomas Express Mixed Endothelial Phenotypes of Blood and Lymphatic Capillaries
Breiteneder-Geleff, S., Soleiman, A., Kowalski, H., Horvat, R., Amann, G., Kriehuber, E., Diem, K., Weninger, W., Tschachler, E., Alitalo, K., et al. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65285-6 · Cited by 1,090
Transforming Growth Factor-β1 Mediates Epithelial to Mesenchymal Transdifferentiation through a RhoA-dependent Mechanism
Bhowmick, N. A., Ghiassi, M., Bakin, A., Aakre, M., Lundquist, C. A., Engel, M. E., Arteaga, C. L., & Moses, H. L. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.1.27 · Cited by 1,004
Rho-Kinase Phosphorylates COOH-terminal Threonines of Ezrin/Radixin/Moesin (ERM) Proteins and Regulates Their Head-to-Tail Association
Matsui, T., Maeda, M., Doi, Y., Yonemura, S., Amano, M., Kaibuchi, K., Tsukita, S., & Tsukita, S. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.3.647 · Cited by 864
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Sander, E. E., ten Klooster, J. P., van Delft, S., van der Kammen, R. A., & Collard, J. G. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.5.1009 · Cited by 831
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Yin, H. L., & Janmey, P. A. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142517 · Cited by 660
Matrix-dependent Tiam1/Rac Signaling in Epithelial Cells Promotes Either Cell–Cell Adhesion or Cell Migration and Is Regulated by Phosphatidylinositol 3-Kinase
Sander, E. E., van Delft, S., ten Klooster, J. P., Reid, T., van der Kammen, R. A., Michiels, F., & Collard, J. G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.5.1385 · Cited by 659
T1 /podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema
Schacht, V. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg342 · Cited by 653
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Peinado, H., Quintanilla, M., & Cano, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211304200 · Cited by 642
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Yonemura, S., Hirao, M., Doi, Y., Takahashi, N., Kondo, T., Tsukita, S., & Tsukita, S. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.4.885 · Cited by 613
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Schacht, V., Dadras, S. S., Johnson, L. A., Jackson, D. G., Hong, Y.-K., & Detmar, M. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62311-5 · Cited by 596
Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway.
Hirao, M., Sato, N., Kondo, T., Yonemura, S., Monden, M., Sasaki, T., Takai, Y., Tsukita, S., & Tsukita, S. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.1.37 · Cited by 593
Tumor invasion in the absence of epithelial-mesenchymal transition: Podoplanin-mediated remodeling of the actin cytoskeleton
Wicki, A., Lehembre, F., Wick, N., Hantusch, B., Kerjaschki, D., & Christofori, G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.010 · Cited by 579
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Yu, Y., Khan, J., Khanna, C., Helman, L., Meltzer, P. S., & Merlino, G. (2004) · Nature Medicine · doi:10.1038/nm966 · Cited by 525
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Williams, M. C., Cao, Y. X., Hinds, A., Rishi, A. K., & Wetterwald, A. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.14.6.8652186 · Cited by 143
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Takahashi, K., Sasaki, T., Mammoto, A., Hotta, I., Takaishi, K., Imamura, H., Nakano, K., Kodama, A., & Takai, Y. (1998) · Oncogene · doi:10.1038/sj.onc.1201874 · Cited by 119
Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis
Gandarillas, A., Scholl, F. G., Benito, N., Gamallo, C., & Quintanilla, M. (1997) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(199709)20:1<10::aid-mc3>3.0.co;2-m · Cited by 102
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Zimmer, G., Oeffner, F., von Messling, V., Tschernig, T., Gröne, H., Klenk, H., & Herrler, G. (1999) · Biochemical Journal · doi:10.1042/0264-6021:3410277 · Cited by 93
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Scholl, F. G., Gamallo, C., & Quintanilla, M. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780185 · Cited by 54
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Kotani, M., Tajima, Y., Osanai, T., Irie, A., Iwatsuki, K., Kanai‐Azuma, M., Imada, M., Kato, H., Shitara, H., Kubo, H., et al. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10696 · Cited by 18

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See all 379

Authors: Martín-Villar, E., Megías, D., Castel, S., Yurrita, M. M., Vilaró, S., & Quintanilla, M.
Venue: Journal of Cell Science
Publisher: The Company of Biologists
Published: 2006-11-01
Volume: 119
Issue: 21
Pages: 4541-4553
ISSN: 0021-9533 (ISSN-L)
1477-9137
DOI: 10.1242/jcs.03218
OpenAlex: W2084558110
Cited by: 379
References: 50
FWCI: 4.67
Type: journal article
Language: en
Open access: green

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Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition

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