The breast cancer susceptibility FGFR2 provides an alternate mode of HER2 activation
Authors: S L Asa
S Serra
W Wei
S Ezzat
W Liu
Journal: Oncogene (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FGFR2; breast cancer risk; HER2; signaling; ADAM10
Affiliations: 1] Department of Medicine, University Health Network, Toronto, Ontario, Canada [2] Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada., 1] Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada [2] Department of Pathology, University Health Network, Toronto, Ontario, Canada.

Abstract:  Fibroblast growth factor receptor 2 (FGFR2) has been shown reproducibly in genome-wide association studies to be associated with increased breast cancer risk. Here we show that mouse mammary tumor virus-neu mice develop breast carcinomas with FGFR2 immunoreactivity that parallels HER2 expression. FGFR2 signaling promotes HER2 shedding through the metalloprotease ADAM10 leading to intracellular accumulation of the truncated p95HER2 protein. This is accompanied by enhanced HER2 signaling and diminished sensitivity to trastuzumab. Functionally, FGFR2 facilitates HER2-mediated cell proliferation, acinar growth in three-dimensional morphogenesis assays and promotes tumor progression in mouse xenografts. These data implicate FGFR2 in a novel mechanism of ErbB activation and demonstrate an important interaction between FGFR2 and HER2 in promoting breast cancer progression.Oncogene advance online publication, 2 February 2015; doi:10.1038/onc.2014.440. 

Retracted: No

PubPeer comments:
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 Yet another judicial review supports the findings of the University Health Network internal investigation committees concerning material non-compliance with accepted research standards by Drs Asa and Ezzat. http: www.counsel-toronto.com success-at-divisional-court-in-research-misconduct-case Asa v. University Health Network, 2017 ONSC 4287 Divisional Court File No.: 018 17 Perhaps now that the courts have dismissed the application for judicial review, Oncogene can finally be provided with findings so this article, which has sat in the advance online publication section for over two years, can finally be properly assessed and its adequacy reviewed, in light of the image irregularities noted above by Paul Brookes. , 
 Letter sent by email to Justin Stebbing and George Miller asking for action on this paper in accordance with COPE guidelines on October 24, 2017. https: www.nature.com onc editors Unfortunately, as yet no reply nor action, and as noted by readers at Retraction Watch http: retractionwatch.com 2017 10 26 dog-ate-data-eight-excuses-editors-hear Justin Stebbing has several problematic papers, e.g. https: pubpeer.com publications 1CCAC58543784D1B17C8416A6D97C2 https: pubpeer.com publications 47CFEDD17549A3F59BAD66BA37FFB9 https: pubpeer.com publications 24909178 so is currently listed in the  Problematic data from editors-in-chief topic https: pubpeer.com topics 1 631E6AF6F96933B7B9946C90F1D23B Meanwhile this paper continues to garner more citations. Problematic papers not dealt with by problematic editors. Most unfortunate that scientific publishing is so tarnished at this point. , 
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 #14 the rotation is particularly odd given that some of the background dots are reproducible in the same position between all but one of the panels. I linked some of the background dots with red lines and then copy-pasted from the 1st panel onto the other panels. I linked some of the duplicated cells in the EGF panel in yellow and then copy pasted onto the FGF7 panel to show the rotation of the cell group (anchored at left most cell) ![file] ,