基因君官网
2015年6月17日 讯 /生物谷BIOON/ –一种特殊的人类基因突变体或可使乳腺癌细胞变得更加具有攻击性，从而使得乳腺癌细胞不仅对化疗产生耐药，而且使得原发性肿瘤开始扩散；近日来自维也纳医科大学的研究人员通过研究发现，名为AF1q的基因或可使得乳腺癌细胞变得更加具有侵略性，同时该基因或许也可以作为一种新型靶点来帮助开发治疗乳腺癌的靶向性疗法。
人类机体的AF1q基因是在染色体异常时发现的，而且该基因被认为是白血病发生的重要因子，同时研究者在急性髓性白血病中发现AF1q基因的水平较高。目前AF1q基因在人类机体中的功能并没有被完全阐明，但本文研究却首次发现AF1q基因是TCF7/Wnt信号通路中的关键蛋白，其可以控制癌细胞的行为，该基因表达的增加会促进肿瘤细胞的发育和生长，同时会抑制天然的细胞死亡，而AF1q基因显著表达的乳腺癌患者往往预后较差，而且AF1q基因阳性的癌细胞对化疗更容易产生耐受性。
后期研究中，研究者发现乳腺癌细胞中AF1q的表达会促进癌细胞在肝脏和肺脏中的转移，当研究者将原发性的肿瘤样本同转移性的样本进行对比后发现，AF1q阳性的癌细胞会不断发生转移，而且目前有很多研究证据表明，AF1q高度表达的癌细胞或可作为癌症转移的专项细胞来进行工作，这些癌细胞可以迁移到机体的其它部位建立肿瘤组织并且进一步扩散。
因此AF1q基因表达的增加或许可以作为预测癌症患者预后较差的一个指标，然而AF1q同时也可以被用于作为开发新型疗法的靶点，后期研究人员还将通过更为深入的研究来阐明该基因为何会促进乳腺癌细胞发生转移，同时他们还将开发新型的靶向个体化疗法来有效抑制乳腺癌的转移。（基因宝jiyinbao.com）
本文系生物谷原创编译整理，欢迎转载！转载请注明来源并附原文链接。更多资讯请下载生物谷APP.
AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis
Jino Park1, Michaela Schlederer2,12, Martin Schreiber3, Ryan Ice4,5, Olaf Merkel6, Martin Bilban7, Sebastian Hofbauer3, Soojin Kim1, Joseph Addison4,5, Jie Zou8, Chunyan Ji8, Silvia T. Bunting9, Zhengqi Wang9, Menachem Shoham10, Gang Huang11, Zsuzsanna Bago-Horvath12, Laura F. Gibson4, Yon Rojanasakul4,13, Scot Remick4, Alexey Ivanov4,5, Elena Pugacheva4,5, Kevin D. Bunting9, Richard Moriggl2,14, Lukas Kenner2,12,15,* and William Tse1,*
AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent “metastatic founder cells” which have invasive properties.