9518

GDF15

Growth differentiation factor-15 (GDF15), a member of the TGF-beta superfamily, affects tumor biology of certain cancers, but remains poorly understood in bladder cancer cells. This study determined the expression, regulation, function, and potential downstream target genes of GDF15 in bladder carcinoma cells. The transitional papilloma carcionoma cells (RT4) expressed higher levels of GDF15 as compared with the bladder carcinoma cells (HT1376 and T24). Treatments of recombinant human GDF15 (rhGDF15) reduced the proliferations of HT1376 and T24 cells. expression of GDF15 was upregulated via DNA demethylation and p53. The cell proliferation, invasion, and tumorigenesis were reduced in ectopic overexpression of GDF15, while enhanced in GDF15 knockdown. The expressions of mammary serine protease inhibitor (MASPIN) and N-myc downstream-regulated family genes (NDRG1, NDRG2, and NDRG3) were upregulated by GDF15 overexpressions and rhGDF15 treatments in bladder carcinoma cells. GDF15 knockdown induced epithelial-mesenchymal transition (EMT) and F-actin polarization in HT1376 cells. Our results suggest that enhanced expressions of MASPIN and N-myc downstream-regulated family genes and the modulation of EMT may account for the inhibitory functions of GDF15 in the cell proliferation, invasion, and tumorigenesis of bladder carcinoma cells. The GDF15 should be considered as a tumor suppressor in human bladder carcinoma cells.

Metastasis is the major cause of cancer deaths, and the epithelial-mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-beta receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily that has been associated with colorectal cancers (CRC). However, the role of GDF15 in the progression of CRC remains unknown. We demonstrated that GDF15 expression was higher in fresh CRC tissues than in adjacent normal tissues. Moreover, we found that GDF15 overexpression significantly facilitated cell viability, cell invasion and migration (p < .01 or p < .05). The protein expression of N-cadherin, vimentin and Twist1 were up-regulated by GDF15 overexpression, while E-cadherin was down-regulated. Reciprocally, using a GDF15-shRNA strategy, we observed that GDF15 downregulation inhibited both basal and GDF16-induced cell viability, invasion and migration in LoVo cells. In conclusion, GDF15 could promote cell viability, invasion and migration of LoVo cells through EMT induction.