當(dāng)?shù)鞍踪|(zhì)RalA和RalB存在時(shí),，細(xì)胞會(huì)以促進(jìn)癌癥侵襲性的形式復(fù)制,。然而到現(xiàn)在為止，還沒(méi)有研究探討了人類癌癥中RAL蛋白的影響,，這對(duì)開(kāi)發(fā)靶向這些蛋白質(zhì)藥物非常重要,。近日，刊登在Cancer Research雜志上的一項(xiàng)研究表明蛋白質(zhì)RalA和RalB的存在與腫瘤的侵襲性特征有關(guān),。
科羅拉多州癌癥中心大學(xué)和論文的主要作者Dan Theodorescu說(shuō)：但這些蛋白的存在與否并非能預(yù)測(cè)侵襲性癌癥的特征,。
RalA和RalB會(huì)導(dǎo)致癌基因級(jí)聯(lián)（基因表達(dá)）變化。Theodorescu和他的同事們發(fā)現(xiàn)了這些變化的標(biāo)記物,，基因的上調(diào)和降低可以預(yù)測(cè)侵襲性癌癥,。
Theodorescu說(shuō)：這些RAL蛋白質(zhì)本身并不促進(jìn)癌癥發(fā)展，但RAL蛋白質(zhì)會(huì)導(dǎo)致基因變化進(jìn)而驅(qū)動(dòng)癌癥的發(fā)生發(fā)展,。
Theodorescu解釋：GTP酶家族的RAL是當(dāng)前已知的RAS癌基因家族成員,。這些Ras家族GTP酶在白血病、肺癌,、結(jié)腸癌和其他癌癥類型中都存在,，研究人員一直努力尋找針對(duì)性的癌癥療法的靶標(biāo)，我們認(rèn)為RAL家庭就是一個(gè)好的癌癥治療靶點(diǎn),。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3966
PMC:
PMID:
Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer
Steven C Smith, Alexander S Baras, Charles R Owens, Garrett Dancik, and Dan Theodorescu,*
RalA and RalB are small GTPases which support malignant development and progression in experimental models of bladder, prostate and squamous cancer. However, demonstration of their clinical relevance in human tumors remains lacking. Here, we developed tools to evaluate Ral protein expression, activation and transcriptional output and evaluated their association with clinicopathologic parameters in common human tumor types. In order to evaluate the relevance of Ral activation and transcriptional output, we correlated RalA and RalB activation with the mutational status of key human bladder cancer genes. We also identified and evaluated a "transcriptional signature" of genes that correlates with depletion of RalA and RalB in vivo. The Ral transcriptional signature score, but not protein expression as evaluated by immunohistochemistry, predicted disease stage, progression to muscle invasion, and survival in human bladder cancers, and metastatic and stem cell phenotypes in bladder cancer models. In prostate cancer, the Ral transcriptional signature score was associated with seminal vesicle invasion, androgen-independent progression, and reduced survival. In squamous cell carcinoma, this score was decreased in cancer tissues compared with normal mucosa, validating the experimental findings that Ral acts as a tumor-suppressor in this tumor type. Together, our findings demonstrate the clinical relevance of Ral in human cancer and provide a rationale for the development of Ral-directed therapies
