Specificity proteins (SPs) have pro‐oncogenic functions in cancer cells, ranging from cancer cell proliferation, migration, invasion, and angiogenesis. There is strong evidence that several antineoplastic drugs target depletion of SP proteins via different pathways. However, the mode of action of SP3 and the underlying consequences of its depletion are not well understood. Here, we demonstrate that SP3 is overexpressed in invasive breast cancer cells vs normal counterparts. The gene expression analysis from The Cancer Genome Atlas datasets indicated that SP3 is strongly correlated with Akt signalling‐related proteins, G protein subunit alpha 13, and RAB33B (RAB33B, member RAS oncogene family). RNA interference of SP3 decreased active phosphorylation of Akt at serine and threonine sites. These findings indicate that SP3 exhibits a pro‐oncogenic function, which clearly fits the description of an nononcogene addiction gene. Future analyses are prompted to uncover the SP3 gene regulation function and to reveal downstream targets of SP3 in breast cancer.

中文翻译：

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SP3与MDA‐MB‐231乳腺癌细胞中的迁移，侵袭和Akt / PKB信号传导相关

特异性蛋白（SP）在癌细胞中具有促癌作用，范围从癌细胞的增殖，迁移，侵袭和血管生成。强有力的证据表明，几种抗肿瘤药通过不同途径靶向消耗SP蛋白。但是，对SP3的作用方式及其耗竭的潜在后果还知之甚少。在这里，我们证明了SP3在浸润性乳腺癌细胞中相对于正常对应细胞过度表达。癌症基因组图谱数据集的基因表达分析表明，SP3与Akt信号相关蛋白，G蛋白亚基α13和RAB33B（RAB33B，RAS癌基因家族成员）密切相关。SP3的RNA干扰降低了丝氨酸和苏氨酸位点Akt的活性磷酸化。这些发现表明，SP3具有致癌作用，显然符合非致癌基因成瘾基因的描述。提示将来进行分析以揭示SP3基因的调控功能并揭示乳腺癌中SP3的下游靶标。