Int J Biochem Mol Biol 2013;4(2):83-94

Original Article
TMEFF2 modulates the AKT and ERK signaling pathways

Xiaofei Chen, Maria J Ruiz-Echevarría

Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, USA; Department of
Oncology, Brody School of Medicine at East Carolina University, Greenville, NC, USA; Lineberger Comprehensive Cancer Center, University of
North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Anatomy and Cell Biology, Brody School of Medicine at East Carolina
University, Greenville, NC, USA

Received June 24, 2013; Accepted July 9, 2013; Epub July 29, 2013; Published August 15, 2013

Abstract: The transmembrane protein with epidermal growth factor (EGF) and two follistatin (FS) motifs 2 (TMEFF2) has a limited tissue
distribution with strong expression only in brain and prostate. While TMEFF2 is overexpressed in prostate cancer indicating an oncogenic role,
several studies indicate a tumor suppressor role for this protein. This dual mode of action is, at least in part, the result of
metalloproteinase-dependent shedding that generates a soluble TMEFF2 ectodomain with a growth promoting function. While recent studies
have shed some light on the biology of different forms of TMEFF2, little is known about the molecular mechanisms that influence its
oncogenic/tumor suppressive function. In several non-prostate cell lines, it has been shown that a recombinant form of the TMEFF2
ectodomain can interact with platelet derived growth factor (PDGF)-AA to suppress PDGF receptor signaling and can promote ErbB4 and
ERK1/2 phosphorylation. However, the role of the full length TMEFF2 in these pathways has not been examined. Using prostate cell lines, here
we examine the role of TMEFF2 in ERK and Akt activation, two pathways implicated in prostate cancer progression and that have been shown
to cross talk in several cancers. Our results show that different forms of TMEFF2 distinctly affect Akt and ERK activation and this may contribute
to a different cellular response of either proliferation or tumor suppression. (IJBMB1306003).

Keywords: Prostate cancer, signaling pathways, Akt, ERK, phosphorylation, TMEFF2

Address correspondence to: Dr. Maria J Ruiz Echevarria, Department of Oncology, Hematology/Oncology, Brody School of Medicine 3E-127,
East Carolina University, 600 Moye Bldv. Greenville, NC 27834. Tel: 252-744-2856; Fax: 252-744-3418; E-mail: