Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.
J Proteome Res. 2010 Oct 1;9(10):4897-905. doi: 10.1021/pr100712t.
To better understand the role of PRL-3 in progression and metastasis of colorectal cancer (CRC), we searched for PRL-3 associated proteins using proteomic methods. We identified 39 PRL-3 associated proteins based on proteomic strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines and CRC tissues indicated that PRL-3 could interact with stathmin. And, both stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells. Moreover, gain-of-function and loss-of-function analyses revealed that stathmin promoted proliferation, cell adhesion, and migration of human CRC cells. Immunohistochemical analysis of 149 colorectal tumor samples showed that overexpression of stathmin was strongly correlated with tumor differentiation (P = 0.035), tumor invasion (P = 0.024), lymph node status (P < 0.001), Dukes classification (P < 0.001), and TNM staging (P < 0.001) of CRC patients. Univariate and multivariate survival analyses further supported that overexpression of stathmin protein was a potential independent poor prognostic factor for CRC. Our results reveal many PRL-3 associated proteins for the first time. The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC.
为了更好地了解 PRL-3 在结直肠癌（CRC）进展和转移中的作用，我们使用蛋白质组学方法寻找与 PRL-3 相关的蛋白。我们根据蛋白质组学策略确定了 39 个与 PRL-3 相关的蛋白。微管蛋白稳定蛋白 stathmin 是一种关键的癌蛋白，被证明是一种新的 PRL-3 相关蛋白。值得注意的是，内源性 CRC 细胞系和 CRC 组织中的共免疫沉淀实验表明，PRL-3 可以与 stathmin 相互作用。并且，stathmin 和 PRL-3 都有助于 CRC 细胞微管（MT）的不稳定。此外，功能获得和功能丧失分析表明，stathmin 促进了人 CRC 细胞的增殖、细胞黏附和迁移。对 149 例结直肠肿瘤样本的免疫组织化学分析表明，stathmin 的过表达与肿瘤分化（P = 0.035）、肿瘤侵袭（P = 0.024）、淋巴结状态（P < 0.001）、Dukes 分类（P < 0.001）和 TNM 分期（P < 0.001）强烈相关。单因素和多因素生存分析进一步支持 stathmin 蛋白的过表达是 CRC 的一个潜在独立不良预后因素。我们的研究结果首次揭示了许多与 PRL-3 相关的蛋白。癌蛋白 stathmin 作为 PRL-3 的一个新靶点，在 CRC 中发挥关键作用。PRL-3 与 stathmin 之间的相互作用导致 CRC 细胞 MT 的不稳定，这有助于 CRC 的进展和转移。
