Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Jinzhou Medical University, 3 Songpo Road, Jinzhou, Liaoning Province 121000, PR China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Jinzhou Medical University, 3 Songpo Road, Jinzhou, Liaoning Province 121000, PR China.
Cell Signal. 2019 Jul;59:171-181. doi: 10.1016/j.cellsig.2019.04.002. Epub 2019 Apr 3.
Microspherule protein 1(MCRS1) is known to be an oncogene in several tumors. However, recent studies have shown that MCRS1 inhibits lymphatic metastasis in gastric cancer (GC) patients by inhibiting telomerase activity. Protein kinase, membrane associated tyrosine/threonine 1(Pkmyt1), a member of the WEE1 family, has been found to interact with MCRS1 by yeast two-hybrid assay; however, how these two proteins interact in GC is still unclear. Hence, this study aimed to investigate the effect of MCRS1 interaction with Pkmyt1 on GC cell proliferation, migration, and invasion. Initially, we observed increased expression of MCRS1 in GC SGC-7901 cells and decreased expression in GC BGC-823 cells. Hence, we down-regulated MCRS1 expression in SGC-7901 cells and up-regulated it in BGC-823 cells. Our results showed that overexpression of MCRS1 inhibits the growth, invasion and migration of GC cells, while downregulation of MCRS1 promotes the growth, invasion and migration of GC cells. When MK1775, an inhibitor of WEE1 kinase, was added after downregulation of MCRS1, phenotypic recovery effects were observed. Overexpression of MCRS1 also inhibited the expression of Pkmyt1 and vice versa. This indicated that there might be a possible interaction between MCRS1 and Pkmyt1. Furthermore, immunoprecipitation assay revealed the interaction between MCRS1 and Pkmyt1 in virto, and immunofluorescence experiments showed that the two proteins were co-localized in the cytoplasm. In conclusion, our study confirmed the specific tumor suppressive activity of MCRS1 in GC proliferation, invasion and migration and suggested that it might inhibit the progression of GC through its interaction with Pkmyt1.
微球体蛋白 1（MCRS1）在几种肿瘤中被认为是一种癌基因。然而，最近的研究表明，MCRS1 通过抑制端粒酶活性抑制胃癌（GC）患者的淋巴转移。蛋白激酶，膜相关酪氨酸/苏氨酸 1（Pkmyt1），WEE1 家族的一员，已通过酵母双杂交试验发现与 MCRS1 相互作用；然而，这两种蛋白质在 GC 中的相互作用仍不清楚。因此，本研究旨在探讨 MCRS1 与 Pkmyt1 相互作用对 GC 细胞增殖、迁移和侵袭的影响。最初，我们观察到 MCRS1 在 GC SGC-7901 细胞中的表达增加，在 GC BGC-823 细胞中的表达减少。因此，我们下调了 SGC-7901 细胞中的 MCRS1 表达，并上调了 BGC-823 细胞中的 MCRS1 表达。结果表明，过表达 MCRS1 抑制 GC 细胞的生长、侵袭和迁移，而下调 MCRS1 促进 GC 细胞的生长、侵袭和迁移。在用 WEE1 激酶抑制剂 MK1775 下调 MCRS1 后添加时，观察到表型恢复效应。过表达 MCRS1 还抑制了 Pkmyt1 的表达，反之亦然。这表明 MCRS1 和 Pkmyt1 之间可能存在相互作用。此外，免疫沉淀试验显示了 MCRS1 和 Pkmyt1 在体外的相互作用，免疫荧光实验显示这两种蛋白质在细胞质中共定位。总之，我们的研究证实了 MCRS1 在 GC 增殖、侵袭和迁移中的特定肿瘤抑制活性，并表明它可能通过与 Pkmyt1 的相互作用抑制 GC 的进展。
