Kravchenko Dmitry Sergeevich, Ivanova Anna Evgenyevna, Podshivalova Elizaveta Sergeevna, Chumakov Stepan Petrovich
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Oncotarget. 2020 Jan 7;11(1):22-30. doi: 10.18632/oncotarget.27410.
RIL/PDLIM4 gene was identified as a tumor suppressor, its expression is frequently altered in various types of malignancies. The product of RIL/PDLIM4 gene is an adapter protein involved in the actin cytoskeleton remolding and assembly of stress fibers crucial for cell motility and epithelial-mesenchymal transition. Although the exact mechanism tethering RIL to cancer development remains unknown some pieces of evidence suggest that RIL may act by suppressing activation of the proto-oncogene tyrosine-protein kinase Src. To further explore this issue we tested how different expression levels of RIL affected the activity of Src in breast cancer cell lines. RIL was ectopically overexpressed in the cell cultures with its relatively low endogenous level, or, otherwise, was downregulated by RNA interference. Whereas we observed no correlation between expression levels of RIL and activity of Src we found that in several cell lines elevated levels of RIL were associated with higher cell migratory activity along with the increased incidence of breast xenograft formation and metastasizing. The obtained data suggest that in some breast cancer models RIL may not act as Src kinase inhibitor, but rather play the role of a potential oncogene that promotes cell motility and contributes to cancer cells spreading.
RIL/PDLIM4基因被鉴定为一种肿瘤抑制因子，其表达在各种类型的恶性肿瘤中经常发生改变。RIL/PDLIM4基因的产物是一种衔接蛋白，参与肌动蛋白细胞骨架重塑以及应激纤维的组装，而应激纤维对于细胞运动和上皮-间质转化至关重要。尽管将RIL与癌症发展联系起来的确切机制尚不清楚，但一些证据表明，RIL可能通过抑制原癌基因酪氨酸蛋白激酶Src的激活而起作用。为了进一步探讨这个问题，我们测试了RIL的不同表达水平如何影响乳腺癌细胞系中Src的活性。在其内源水平相对较低的细胞培养物中异位过表达RIL，或者通过RNA干扰将其下调。虽然我们没有观察到RIL的表达水平与Src的活性之间存在相关性，但我们发现，在几个细胞系中，RIL水平升高与更高的细胞迁移活性相关，同时乳腺异种移植形成和转移的发生率增加。获得的数据表明，在一些乳腺癌模型中，RIL可能不是作为Src激酶抑制剂起作用，而是发挥潜在癌基因的作用，促进细胞运动并导致癌细胞扩散。
