Jiangsu Breast Disease Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
Oncol Rep. 2018 Aug;40(2):704-714. doi: 10.3892/or.2018.6482. Epub 2018 Jun 7.
Fibroblast growth factor 18 (FGF18) increases cell motility and invasion in colon tumors, and is linked with ovarian and lung tumors. Furthermore, the increased expression of FGF18 mRNA and protein has been associated with poor overall survival in cancer patients. However, its function has not been investigated in breast cancer. In the present study, we demonstrated that FGF18 promoted cell growth and metastasis in vitro and stimulated tumor growth in xenograft models in vivo. FGF18 mediated the proliferation of MDA‑MB‑231 cells via the ERK/c‑Myc signaling pathway and induced epithelial‑to‑mesenchymal transition (EMT) factors to promote cancer migration and invasion. The decreased expression of FGF18 was strongly correlated with the loss/reduction of p‑ERK, c‑Myc, N‑cadherin, vimentin and Snail 1 protein in MDA‑MB‑231 cells. Collectively, our results indicated that FGF18 played an important role in the growth and metastasis of breast cancer via the ERK/c‑Myc signaling pathway and EMT, indicating that FGF18 may be a potential molecular treatment target for breast cancer.
成纤维细胞生长因子 18(FGF18)可增加结肠肿瘤细胞的迁移和侵袭能力,并与卵巢癌和肺癌相关。此外,FGF18mRNA 和蛋白的高表达与癌症患者的总体生存率降低相关。然而,其在乳腺癌中的功能尚未得到研究。在本研究中,我们证明了 FGF18 可促进体外细胞生长和转移,并在体内异种移植模型中刺激肿瘤生长。FGF18 通过 ERK/c-Myc 信号通路介导 MDA-MB-231 细胞的增殖,并诱导上皮-间充质转化(EMT)因子促进癌症迁移和侵袭。FGF18 的表达下调与 MDA-MB-231 细胞中 p-ERK、c-Myc、N-钙黏蛋白、波形蛋白和 Snail 1 蛋白的缺失/减少密切相关。综上所述,我们的研究结果表明,FGF18 通过 ERK/c-Myc 信号通路和 EMT 途径在乳腺癌的生长和转移中发挥重要作用,表明 FGF18 可能是乳腺癌潜在的分子治疗靶点。