Cancer Res：蛋白质RAL与肿瘤的侵袭性特征有关

当蛋白质RalA和RalB存在时，细胞会以促进癌症侵袭性的形式复制。然而到现在为止，还没有研究探讨了人类癌症中RAL蛋白的影响，这对开发靶向这些蛋白质药物非常重要。近日，刊登在Cancer Research杂志上的一项研究表明蛋白质RalA和RalB的存在与肿瘤的侵袭性特征有关。

科罗拉多州癌症中心大学和论文的主要作者Dan Theodorescu说：但这些蛋白的存在与否并非能预测侵袭性癌症的特征。

RalA和RalB会导致癌基因级联（基因表达）变化。Theodorescu和他的同事们发现了这些变化的标记物，基因的上调和降低可以预测侵袭性癌症。

Theodorescu说：这些RAL蛋白质本身并不促进癌症发展，但RAL蛋白质会导致基因变化进而驱动癌症的发生发展。

Theodorescu解释：GTP酶家族的RAL是当前已知的RAS癌基因家族成员。这些Ras家族GTP酶在白血病、肺癌、结肠癌和其他癌症类型中都存在，研究人员一直努力寻找针对性的癌症疗法的靶标，我们认为RAL家庭就是一个好的癌症治疗靶点。（生物谷：Bioon.com）

doi:10.1158/0008-5472.CAN-11-3966
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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