Epidermal Growth Factor Receptor Distribution during Chemotactic Responses

Bailly, Maryse; Wyckoff, Jeffrey; Bouzahzah, Boumediene; Hammerman, Ross; Sylvestre, Vonetta; Cammer, Michael; Pestell, Richard G.; Segall, Jeffrey E.

doi:10.1091/mbc.11.11.3873

Cited by 81 publications

(62 citation statements)

References 34 publications

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“…Under quiescent conditions, the EGFR was localized primarily at the cell surface (Figure 8a). Exposure of the cells to EGF evoked a rapid mobilization of the receptor into cytoplasmic vesicles (Figure 8b), in agreement with previous studies (Carter and Sorkin, 1998;Bailly et al, 2000;Carpenter, 2000). In contrast, exposure of the cells to either recombinant protein did not cause any appreciable EGFR movement into the cytoplasm (Figure 8c-f).…”

Section: Lrig1 Induces Neither Egfr Internalization Nor Egfr Phosphorsupporting

confidence: 91%

“…It has been previously shown that this EGFR, carrying either a GFP or a CFP, is fully viable and signals in response to EGF, and has been successfully used to study EGFR endocytosis, trafficking and interaction with various adaptor proteins (Carter and Sorkin, 1998;Sorkin et al, 2000;Jiang and Sorkin, 2002;Jiang et al, 2003) and chemotactic responses (Bailly et al, 2000). Immunoblotting of total cell lysates showed the expression of a B200-kDa EGFR-CFP chimera in the CHO-K1 11A3 cells ( Figure 4c).…”

Section: Lrig1 Ectodomain Attenuates Egfr Activity S Goldoni Et Almentioning

confidence: 83%

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A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity

et al. 2006

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Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligandindependent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (K d ¼ 10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growthpromoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.

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Section: Lrig1 Induces Neither Egfr Internalization Nor Egfr Phosphorsupporting

confidence: 91%

Section: Lrig1 Ectodomain Attenuates Egfr Activity S Goldoni Et Almentioning

confidence: 83%

A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity

et al. 2006

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“…Western blots, immunofluorescence and fluorescenceactivated cell sorting (FACS) confirm that MTLn3 cells express ErbB2, ErbB3 (Levea et al, 2000;Xue et al, 2006; Kedrin et al, 2009) and ErbB4 (personal communication Sumanta Goswami, Yeshiva University, and Michele Balsamo, MIT, Cambridge, MA). Previous studies have also confirmed that EGFRs in MTLn3 cells are fully active and homogenously distributed on the plasma membrane (Lichtner et al., 1992;Bailly et al, 2000). Dominant coexpression of vimentin and CK14 in MTLn3 cells suggests that these cells represent a myoepithelial or basal cell that has partially dedifferentiated (Lichtner et al, 1991).…”

Section: Cell Linesmentioning

confidence: 78%

Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer

Roussos

Balsamo

Alford

et al. 2011

Journal of Cell Science

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172

255

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SummaryWe have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (Mena INV ) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated Mena INV increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by Mena INV is dependent on a macrophage-tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of Mena INV and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells. Journal of Cell Science metastatic progression. Mena is a member of the Ena/VASP family of proteins and binds actin to regulate the geometry and assembly of filament networks through: (1) an anti-capping protein activity (Bear et al., 2002;Barzik et al., 2005; Hansen and Mullins, 2010) that involves binding to profilin and both G-and F-actin; (2) Mena tetramerization, and (3) reduction in the density of actin-related proteins 2 and 3 (Arp2/3)-mediated branching (Gertler et al., 1996;Barzik et al., 2005;Ferron et al., 2007;Pasic et al., 2008;Bear and Gertler, 2009; Hansen and Mullins, 2010). Alternative splicing for the Mena gene has been reported: a 19 amino acid residue insertion just after the EVH1 domain generates the Mena invasion isoform (Mena INV , formerly Mena +++ ) (Gertler et al., 1996;Philippar et al., 2008), whereas a 21 residue insertion in the EVH2 domain generates the Mena11a isoform (Di Modugno et al., 2007). A comparison of the invasive and migratory tumor cells collected in vivo, with primary tumor cells isolated from mouse, rat and human cell-line-derived mammary tumors, revealed that Mena INV expression is upregulated and Mena11a is downregulated selectively in the invasive and migrating carcinoma cell population (Goswami et al., 2009). The differential regulation of Mena isoforms across species suggests that these two isoforms have important roles in invasion and metastasis.In previous studies, we showed that expression of Mena INV in a xenograft mouse mammary tumor promotes increased formation of spontaneous lung metastases from orthotopic tumors and alters the sensitivity of tumor cells to epidermal growth factor (EGF) . We undertook the current study to identify the step(s) in the metastatic cascade that are affected by Mena INV expression and investigate the effect of expression of...

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“…The EGF receptor, ErbB1 is involved in the metastatic process. Overexpression of ErbB1 can increase chemotaxis to EGF (Bailly et al, 1998;Bailly et al, 2000;Gschwind et al, 2002;Dittmar et al, 2002). Activation of ErbB2/ErbB3 heterodimers can affect both proliferation and motility (Xue et al, 2006b).…”

Section: Introductionmentioning

confidence: 99%

EGF receptor signalling is essential for electric-field-directed migration of breast cancer cells

McCaig

Cao

et al. 2007

Journal of Cell Science

Self Cite

124

111

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Epidermal Growth Factor Receptor Distribution during Chemotactic Responses

Cited by 81 publications

References 34 publications

A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity

A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity

Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer

EGF receptor signalling is essential for electric-field-directed migration of breast cancer cells

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