轉(zhuǎn)錄因子ZNF217是染色體20q13的擴增候選基因,，20％至30％的原位乳腺癌腫瘤患者都表達轉(zhuǎn)錄因子ZNF217,，ZNF217與乳腺癌患者預后較差呈相關性。
近日刊登在Cancer Discovery上的一則新研究證實,，ZNF217過度表達驅(qū)動腫瘤細胞的異常分化,，激活下游信號級聯(lián)反應，這信號級聯(lián)反應促進腫瘤細胞自我更新能力的提高,、腫瘤細胞的間充質(zhì)標志物表達升高,，細胞運動和轉(zhuǎn)移能力也上調(diào)。
研究人員用硅片篩選發(fā)現(xiàn),，該轉(zhuǎn)錄因子在低濃度時可抑制高表達ZNF217癌癥細胞的生長,。在體內(nèi)研究中，核苷類似物曲西明（Triciribine）抑制ZNF217誘發(fā)的腫瘤生長和化療耐藥,，其機制就是通過抑制如Akt的磷酸化,、絲裂原活化蛋白激酶（MAPK）的磷酸化等信號。
由于在許多癌癥中ZNF217的高表達,，研究數(shù)據(jù)表明ZNF217是一種乳腺癌患者預后差的生物標志物,，在過度表達ZNF217的乳腺癌患者中，曲西明（Triciribine）的治療可能是化治療策略的一個新方法,。（生物谷：Bioon.com）
doi:10.1158/2159-8290.CD-12-0093
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The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression.
Littlepage LE, Adler AS, Kouros-Mehr H, Huang G, Chou J, Krig SR, Griffith OL, Korkola JE, Qu K, Lawson DA, Xue Q, Sternlicht MD, Dijkgraaf GJ, Yaswen P, Rugo HS, Sweeney CA, Collins CC, Gray JW, Chang HY, Werb Z.
The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20% to 30% of primary human breast cancers and that correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We show that the nucleoside analogue triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance and inhibits signaling events [e.g., phospho-AKT, phospho-mitogen-activated protein kinase (MAPK)] in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers.
