AB038. High tropomyosin related kinase (TrkB) expression induces epithelial-mesenchymal transition, anoikis resistance and metastasis in prostatic cancer cells

BACKGROUND: The neurotrophic receptor tropomyosin related kinase (TrkB) is associated with tumor progression in neuroblastoma and certain human malignancies. Recent reports indicate TrkB may participate in the epithelial-mesenchymal transition (EMT). E-cadherin, an important EMT regulator, and three E-cadherin repressors, Twist, Snail and Zeb1, are critical for TrkB to induce EMT. This study investigates whether TrkB induces EMT in PC-3 cells and its possible molecular mechanisms. METHODS: The biological role of TrkB in CRC was analyzed using RNA interference against TrkB in the PC-3 cell line to assess tumor progression and the expression of some proteins key to EMT in vitro and in vivo. RESULTS: In vitro, cell proliferation, colony formation, migration, and invasion were significantly inhibited by TrkB knockdown, while the anoikis rate increased in TrkB siRNA-transfected cells compared to control. After TrkB knockdown, expressions of the proteins key to EMT, including Twist, Snail and Zeb1 in siTrkB were significantly down-regulated; conversely, E-cadherin expression was up-regulated. In vivo, high expression of TrkB promoted tumorigenesis and metastasis in nude mice with prostatic cancer. CONCLUSIONS: High TrkB expression enhances malignant potential in terms of proliferation, migration, invasion, and anoikis resistance in PC-3 cells. These results indicate TrkB could induce EMT and play an important role in prostate cancer progression to metastasis.