Epidermal growth factor stimulation can substitute for c-Src overexpression in promoting breast carcinoma invasion

Lotz, Margaret M.; Wang, Helen H.-F.; Cance, William G.; Matthews, Tokunbo; Pories, Susan E.

doi:10.1016/s0022-4804(02)00100-2

Cited by 13 publications

(10 citation statements)

References 20 publications

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“…In fact, ErbB overexpression correlates with aggressive tumor behavior and metastasis (54,55). Interestingly, previous studies show that SHP2 plays a positive role in cell migration (49,50).…”

Section: Discussionmentioning

confidence: 99%

Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor

Ren

Shao

Mei

et al. 2004

Journal of Biological Chemistry

150

154

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Epidermal growth factor (EGF) induces paxillin tyrosine dephosphorylation and Src activation, but the signaling pathways that mediate these responses were largely undefined. We found that Gab1, a docking protein for the SHP2 protein-tyrosine phosphatase in EGFstimulated cells, was associated with paxillin. SHP2 dephosphorylated paxillin and caused dissociation of Csk, a negative regulator of Src, from paxillin but had no effect on paxillin-Src association. A lower level of Src Tyr-530 phosphorylation was detected in paxillin-associated Src in EGF-stimulated cells. Expression of an SHP2 binding defective mutant of Gab1 (Gab1FF) or a catalytically inactive mutant of SHP2 (SHP2DN) prevented paxillin tyrosine dephosphorylation and Src activation induced by EGF. Importantly, Gab1FF blocked paxillin-SHP2 complex formation, Src Tyr-530 dephosphorylation, Erk activation, and cell migration induced by EGF. Inhibition of Src tyrosine kinase activity abrogated EGF-stimulated Erk activation and cell migration. Together, these results reveal that Gab1 recruits SHP2 to dephosphorylate paxillin, leading to dissociation of Csk from the paxillin-Src complex and Src activation and that Src is an SHP2 effector involved in EGF-stimulated Erk activation and cell migration.

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Section: Discussionmentioning

confidence: 99%

Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor

Ren

Shao

Mei

et al. 2004

Journal of Biological Chemistry

150

154

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“…In vitro studies using human cell lines suggest a role for Egfr/Ras signaling in cell motility and tumour invasion (Krueger et al, 2001;Mahoney et al, 2002;Lotz et al, 2003). We have reported that the Egfr pathway mediates signaling between squamous and columnar epithelia.…”

Section: Discussionmentioning

confidence: 99%

Egfr/Ras pathway mediates interactions between peripodial and disc proper cells inDrosophilawing discs

Pallavi

Shashidhara

2003

Development

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All imaginal discs in Drosophila are made up of a layer of columnar epithelium or the disc proper and a layer of squamous epithelium called the peripodial membrane. Although the developmental and molecular events in columnar epithelium or the disc proper are well understood, the peripodial membrane has gained attention only recently. Using the technique of lineage tracing, we show that peripodial and disc proper cells arise from a common set of precursors cells in the embryo, and that these cells diverge in the early larval stages. However, peripodial and disc proper cells maintain a spatial relationship even after the separation of their lineages. The peripodial membrane plays a significant role during the regional subdivision of the wing disc into presumptive wing, notum and hinge. The Egfr/Ras pathway mediates this function of the peripodial membrane. These results on signaling between squamous and columnar epithelia are particularly significant in the context of in vitro studies using human cell lines that suggest a role for the Egfr/Ras pathway in metastasis and tumour progression.

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“…Similar to FAK research, there are plenty of in vitro data on c-Src and breast carcinoma. Most of the in vitro studies demonstrate that c-Src overexpression and activation are needed for malignant transformation and invasion of breast epithelium [21,22].…”

Section: Discussionmentioning

confidence: 99%

Focal adhesion proteins as markers of malignant transformation and prognostic indicators in breast carcinoma

et al. 2006

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Epidermal growth factor stimulation can substitute for c-Src overexpression in promoting breast carcinoma invasion

Cited by 13 publications

References 20 publications

Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor

Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor

Egfr/Ras pathway mediates interactions between peripodial and disc proper cells inDrosophilawing discs

Focal adhesion proteins as markers of malignant transformation and prognostic indicators in breast carcinoma

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