FGFR2 Isoforms Support Epithelial–Stromal Interactions in Thyroid Cancer Progression
Authors: Shereen Ezzat
Stefano Serra
Miao Guo
Wei Liu
Sylvia L Asa
Journal: Cancer Research (2012)
Discipline: CLINICAL MEDICINE
Keywords: Alternate splicing; fibroblast growth factor receptor; FGFR2-IIIb; FGFR2-IIIc; thyroid cancer
Affiliations: The Ontario Cancer Institute, Department of Medicine, University Health Network, Toronto, Ontario, Canada.

Abstract:  Alternate splicing yields two distinct isoforms of the fibroblast growth factor (FGF) receptor FGFR2-IIIb and FGFR2-IIIc varying their extracellular structure in human thyroid cancer, in which FGFR expression is commonly dysregulated. In this study, we characterized the function of these variants in modulating thyroid cancer behavior. Enforced expression of either FGFR2-IIIb or FGFR2-IIIc in thyroid epithelial cancer cells reduced expression of fibronectin, MAGE-A3 and MMP9, while increasing p21 and enhancing Rb dephosphorylation. Consistent with these tumor-suppressive properties, FGFR2-IIIb and FGFR2-IIIc each diminished invasive behavior in vitro and reduced tumor growth and metastasis in vivo. Notably, these effects contrasted with those produced by expression of these FGFR isoforms in fibroblasts, in which they both stimulated cell growth. Moreover, in xenograft tumors generated by coimplantation of epithelial and fibroblast cells expressing that same isoform, there was no significant effect on tumor progression. Conversely, FGFR2-IIIb expression in epithelial cells yielded higher FGF4/FGF7 expression that, in the presence of FGFR2-IIIc-expressing fibroblasts, enhanced tumor progression. Together, our findings highlight the importance of cellular context in assigning growth properties to growth factor receptor isoforms. More specifically, they show how alternative splicing of FGFR2 yields heteroisoforms critical to the growth-promoting actions of FGFs that exert distinct epithelial-stromal effects in thyroid cancer. 

Retracted: No

PubPeer comments:
 How to explain the flipping in figure 3? , 
 Retraction Watch has obtained the University of Toronto Research Internal Investigation Committee Final Report via a freedom of access to information request https: retractionwatch.com 2018 07 02 reports-of-misconduct-investigations-can-tell-us-a-lot-here-are-more-than-a-dozen-of-them See entry 1. Sylvia Asa and Shereen Ezzat, formerly of the University Health Network, University of Toronto Story: Sanction for Toronto researchers upheld despite court challenge Report The  Report link is https: retractionwatch.com wp-content uploads 2018 06 Ezzat-and-Asa-Final-InternalInvestigationReport-2014-10-15.pdf The report notes many more image irregularities than described above, many of them with conclusion  A satisfactory explanation for these irregularities has not been provided . Regarding the identical images in Fig 3A and 3B, and flipped images in 3C described above, the report notes  The Committee was informed that corrected images had been provided to the journal editor. However, the correction has not been published. Thus even though  corrected images were supplied and some sort of correction generated, the journal still shows no correction, no expression of concern or any other clue that problems exist for this paper. So much for editorial concern at Cancer Research. Most unfortunate that science sits in the hands of such disinterested editors. , 
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 Additional concern identified by another reader. Journal notified (again, apparently). *** ![file] ,