A truncated isoform of TMEFF2 encodes a secreted protein in prostate cancer cells.
The transmembrane protein TMEFF2, also known as tomoregulin or TENB2, has been proposed as a potential immunotherapeutic target for the treatment of prostate cancer. Much attention has focused on its limited tissue distribution, with strong expression seen only in the brain and the prostate. Here we describe the identification of a novel splice variant of TMEFF2 expressed both in the normal prostate and in prostate cancer. This variant encodes an isoform of TMEFF2 that is truncated after the first four coding exons, eliminating both the EGF-like and the transmembrane domains. Fusion of GFP to this isoform demonstrated that this variant transcript produces a truncated TMEFF2 protein (TMEFF2-S). In contrast to full-length TMEFF2-GFP, the truncated TMEFF2-S-GFP fusion protein was enriched in cytosolic granules, showed no staining at the plasma membrane, and was secreted into the medium of transfected cells grown in tissue culture. These results indicate that a truncated isoform of TMEFF2 is expressed from this locus. This secreted form of TMEFF2 may functionally interact with full-length TMEFF2, or its binding partners, and may also influence current immune-based treatment strategies.
Quayle
Steven N
SN
Genome Sciences Centre, British Columbia Cancer Agency, and Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 4E6.
Sadar
Marianne D
MD
D017398:Alternative Splicing; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C423567:TMEFF2 protein, human