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Commentary & View
The EGFR-GEP100-Arf6 pathway in breast cancer: Full invasiveness is not from the inside
Hisataka Sabe, Shigeru Hashimoto, Masaki Morishige, Ari Hashimoto and Eiji Ogawa
volume 2 | issue 2
april/may/june 2008This is an open-access article
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Arf6 and its effector AMAP1 are overexpressed in malignant breast cancer cells, and are involved in their invasion and metastasis. We recently revealed that GEP100, a guanine nucleotide exchanging factor, is responsible for the activation of Arf6 which induces invasion and metastasis. GEP100 associated directly with ligand-activated epidermal growth factor receptor (EGFR) to be activated. Disruption of E-cadherin-mediated cell-cell adhesion is one of the major steps involved in acquisition of invasive phenotypes of most carcinomas. The EGFR-GEP100-Arf6 pathway not only activated matrix invasion activity but also perturbed E-cadherin function. GEP100 was found to be expressed in more than 80% of invasive ductal carcinomas. However, 60% of ductal carcinomas in situ were also positive for GEP100, in which GEP100 was preferentially coexpressed with EGFR in their malignant cases. Microenvionments have been highly implicated in the development of tumor malignancy. Our results reveal an aspect of the precise molecular mechanism of cancer invasion and metastasis, in which full invasiveness is not acquired just by alterations of cancer cells themselves, but their microenvironments may also play pivotal roles.
Authors
Hisataka Sabe
Osaka Bioscience Institute
Shigeru Hashimoto
Osaka Bioscience Institute
Masaki Morishige
Oita University
Ari Hashimoto
Osaka Bioscience Institute
Eiji Ogawa
Kyoto University Hospital
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.