Identification of an AKT-dependent signalling pathway that mediates tamoxifen-dependent induction of the pro-metastatic protein anterior gradient-2.
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.
Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic.
Roman
R
Hrstka
Euan
E
Murray
Veronika
V
Brychtova
Pavel
P
Fabian
Ted R
TR
Hupp
Borivoj
B
Vojtesek
D064413:3-Phosphoinositide-Dependent Protein Kinases; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D035683:MicroRNAs; D008969:Molecular Sequence Data; D009088:Mucoproteins; D015513:Oncogene Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
C502296:AGR2 protein, human; D018931:Antineoplastic Agents, Hormonal; D035683:MicroRNAs; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012263:Ribonucleosides; D013629:Tamoxifen; C023764:triciribine; D012694:Serine; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt