“胃肠道间质瘤” (GISTs)发生在“Cajal间质细胞”中，它们是嵌入在胃肠道肌肉组织中的细胞，在那里它们产生电节律。现在Chi等人发现，转录因子ETV1是这些细胞的发育所必需的，而且该因子还促进肿瘤发育。KIT基因（经常被GIST中的突变激发）在“Cajal间质细胞”的转化中与ETV1配合（部分是通过促进ETV1的稳定性来进行这种配合的）。ETV1似乎在所有GISTs中都以高水平存在，使其成为用于医学诊断的生物标记的一个候选对象，而ETV1阻断药物也可能会被证明对于抗药性GIST有疗效。（生物谷 Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09409
ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours
Ping Chi,Yu Chen,Lei Zhang,Xingyi Guo,John Wongvipat,Tambudzai Shamu,Jonathan A. Fletcher,Scott Dewell,Robert G. Maki,Deyou Zheng,Cristina R. Antonescu,C. David Allis& Charles L. Sawyers
Gastrointestinal stromal tumour (GIST) is the most common human sarcoma and is primarily defined by activating mutations in the KIT or PDGFRA receptor tyrosine kinases1, 2. KIT is highly expressed in interstitial cells of Cajal (ICCs)—the presumed cell of origin for GIST—as well as in haematopoietic stem cells, melanocytes, mast cells and germ cells2, 3. Yet, families harbouring germline activating KIT mutations and mice with knock-in Kit mutations almost exclusively develop ICC hyperplasia and GIST4, 5, 6, 7, suggesting that the cellular context is important for KIT to mediate oncogenesis. Here we show that the ETS family member ETV1 is highly expressed in the subtypes of ICCs sensitive to oncogenic KIT mediated transformation8, and is required for their development. In addition, ETV1 is universally highly expressed in GISTs and is required for growth of imatinib-sensitive and resistant GIST cell lines. Transcriptome profiling and global analyses of ETV1-binding sites suggest that ETV1 is a master regulator of an ICC-GIST-specific transcription network mainly through enhancer binding. The ETV1 transcriptional program is further regulated by activated KIT, which prolongs ETV1 protein stability and cooperates with ETV1 to promote tumorigenesis. We propose that GIST arises from ICCs with high levels of endogenous ETV1 expression that, when coupled with an activating KIT mutation, drives an oncogenic ETS transcriptional program. This differs from other ETS-dependent tumours such as prostate cancer, melanoma and Ewing sarcoma where genomic translocation or amplification drives aberrant ETS expression9, 10, 11. It also represents a novel mechanism of oncogenic transcription factor activation.
