Conclusions
GDF15 promotes ESCC progression by increasing cellular proliferation, migration, and invasion via TGF-βRII signaling.
Methods
Western blotting, MTS, and Transwell migration/invasion assays were used to evaluate cell signaling, proliferation, and migration/invasion, respectively, in ESCC cell lines treated with recombinant human GDF15 (rhGDF15). ESCC cell lines were administered a TGF-βRI/II inhibitor (LY2109761), small interfering RNA against TGF-β type II receptor (TGF-βRII), or neutralizing antibody against TGF-βRII to study the role of TGF-βRII in mediating the effects of rhGDF15. The localization of GDF15 and TGF-βRII in ESCC cell lines was observed by immunofluorescence. TGF-βRII expression in ESCC tissues was analyzed by immunohistochemistry, and the relationship between clinicopathological factors and prognosis in ESCC patients was evaluated.
Results
rhGDF15 increased levels of phosphorylated Akt, Erk1/2, and TGF-βRII in ESCC cell lines. Inhibition/knockdown of TGF-βRII suppressed rhGDF15-induced activation of Akt and Erk1/2 and enhancement of cellular proliferation, migration, and invasion. Immunofluorescence revealed that TGF-βRII and GDF15 were colocalized in ESCC cell lines. High TGF-βRII expression in ESCC tissues, as determined by immunohistochemistry, correlated with depth of invasion and increased number of infiltrating TAMs. ESCC patients with high TGF-βRII expression showed a tendency toward poor prognosis. Conclusions: GDF15 promotes ESCC progression by increasing cellular proliferation, migration, and invasion via TGF-βRII signaling.