Aberrant expression of the transcriptional factor Twist1 promotes invasiveness in ALK-positive anaplastic large cell lymphoma.

摘要: Abstract The transcriptional factor Twist1 has been shown to play a key role in regulating epithelial mesenchymal transition, invasiveness and migratory properties solid tumors. We found that is aberrantly expressed ALK-positive anaplastic large cell lymphoma (ALK + ALCL), type of T-cell lymphoid malignancy. Using RT-PCR Western blots, was detectable all 3 ALK + ALCL lines examined but absent normal T-cells. By immunohistochemistry, 10 cases examined; benign tissues were consistently negative. expression cells can be attributed the NPM-ALK/STAT3 signaling axis, oncogenic driving force this tumor type. biologically important cells, as knockdown resulted significant decrease their an in-vitro assay. Further investigation revealed increase linked activation AKT down-regulation p66Shc, two proteins known involved NPM-ALK-mediated oncogenesis. Lastly, sensitizes growth inhibitory effect PF-2341066 (Crizotinib®), ALK inhibitor being used clinical trials. In conclusion, expression, owing abnormal signaling, contributes its decreased sensitivity ALK + ALCL.