چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| The tumorigenicity of most cases of ALK-positive anaplastic large-cell lymphoma (ALK1 ALCL) is driven by the oncogenic fusion proteinNPM-ALKin a STAT3-dependent manner. Because it has been shown that STAT3 can be inhibited by STAT1 in some experimental models, we hypothesized that the STAT1 signaling pathway is defective in ALK1 ALCL, thereby leaving the STAT3 signaling unchecked. Compared with normal T cells, ALK1 ALCL tumors consistently expressed a low level of STAT1. Inhibition of the ubiquitinproteasome pathway appreciably increased STAT1 expression in ALK1 ALCL cells. Furthermore, we found evidence that NPM-ALK binds to and phosphorylates STAT1, thereby promoting its proteasomal degradation in a STAT3-dependent manner. If restored, STAT1 is functionally intact in ALK1 ALCL cells, because it effectively upregulated interferon-g, induced apoptosis/cell-cycle arrest, potentiated the inhibitory effects of doxorubicin, and suppressed tumor growth in vivo. STAT1 interfered with the STAT3 signaling by decreasing STAT3 transcriptional activity/DNA binding and its homodimerization. The importance of the STAT1/STAT3 functional interaction was further highlighted by the observation that short interfering RNA knockdown of STAT1 significantly decreased apoptosis induced by STAT3 inhibition. Thus, STAT1 is a tumor suppressor in ALK1ALCL. Phosphorylation and downregulation of STAT1 by NPM-ALK represent other mechanisms by which this oncogenic tyrosine kinase promotes tumorigenesis |
| نویسنده | نفر چندم مقاله |
|---|---|
| ام لیلا مولوی | دوم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| STAT1 in blood journal, cover paper.pdf | 1397/08/12 | 2052201 | دانلود |
