Mansour Mohammed A
Division of Human Sciences, School of Applied Sciences, London South Bank University, London, UK.
Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
J Biochem Mol Toxicol. 2021 Mar;35(3):e22657. doi: 10.1002/jbt.22657. Epub 2020 Oct 28.
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.
特异性蛋白（SPs）在癌细胞中具有促癌功能，涉及癌细胞增殖、迁移、侵袭和血管生成等方面。有充分证据表明，几种抗肿瘤药物通过不同途径靶向消耗SP蛋白。然而，SP3的作用模式及其消耗的潜在后果尚未得到充分了解。在此，我们证明SP3在侵袭性乳腺癌细胞中相对于正常细胞过度表达。来自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Akt在丝氨酸和苏氨酸位点的活性磷酸化。这些发现表明，SP3具有促癌功能，这显然符合非癌基因成瘾基因的描述。未来的分析促使我们揭示SP3基因调控功能，并揭示乳腺癌中SP3的下游靶点。
