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Cancer Lett. 2013 Jun 10;333(2):187-93. doi: 10.1016/j.canlet.2013.01.034. Epub 2013 Jan 24.

Identification of an AKT-dependent signalling pathway that mediates tamoxifen-dependent induction of the pro-metastatic protein anterior gradient-2.

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Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic.


The pro-metastatic protein anterior gradient-2 (AGR2) was previously demonstrated as a predictive factor of poor response to tamoxifen treatment. In this study we aimed to delineate the key signalling pathway that may contribute to regulation of AGR2 protein induction in order to identify novel targets to overcome tamoxifen resistance in tumour cells. Together, our data identify PDPK1-AKT as a pro-oncogenic signalling pathway that triggers AGR2 protein induction in response to tamoxifen and suggest that AKT inhibitors could be used as part of a therapeutic strategy to treat tamoxifen resistant, AGR2 over-expressing cancers.

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