National Cancer Institute, Centro di Riferimento Oncologico, Division of Experimental Oncology 2, Via Franco Gallini, 2, 33081 Aviano, Italy.
Expert Opin Ther Targets. 2011 Nov;15(11):1249-66. doi: 10.1517/14728222.2011.620951. Epub 2011 Oct 7.
Stathmin is a microtubule-destabilizing phosphoprotein, firstly identified as the downstream target of many signal transduction pathways. Several studies then indicated that stathmin is overexpressed in many types of human malignancies, thus deserving the name of Oncoprotein 18 (Op18). At molecular level, stathmin depolymerizes microtubules by either sequestering free tubulin dimers or directly inducing microtubule-catastrophe. A crucial role for stathmin in the control of mitosis has been proposed, since both its overexpression and its downregulation induce failure in the correct completion of cell division. Accordingly, stathmin is an important target of the main regulator of M phase, cyclin-dependent kinase 1.
Recent evidences support a role for stathmin in the regulation of cell growth and motility, both in vitro and in vivo, and indicate its involvement in advanced, invasive and metastatic cancer more than in primary tumors.
Many studies suggest that high stathmin expression levels in cancer negatively influence the response to microtubule-targeting drugs. These notions together with the fact that stathmin is expressed at very low levels in most adult tissues strongly support the use of stathmin as marker of prognosis and as target for novel anti-tumoral and anti-metastatic therapies.
Stathmin 是一种微管解聚磷酸化蛋白,最初被鉴定为许多信号转导途径的下游靶点。随后的几项研究表明,Stathmin 在许多人类恶性肿瘤中过度表达,因此被称为癌蛋白 18(Op18)。在分子水平上,Stathmin 通过隔离游离微管二聚体或直接诱导微管崩溃来解聚微管。Stathmin 在控制有丝分裂中起着至关重要的作用,因为它的过表达和下调都会导致细胞分裂的正确完成失败。因此,Stathmin 是有丝分裂主要调节因子——细胞周期蛋白依赖性激酶 1 的重要靶点。
最近的证据支持 Stathmin 在细胞生长和运动的调节中的作用,无论是在体外还是体内,并表明它在晚期、侵袭性和转移性癌症中的作用大于原发性肿瘤。
许多研究表明,癌症中高表达的 Stathmin 水平会对微管靶向药物的反应产生负面影响。这些观点以及 Stathmin 在大多数成人组织中表达水平极低的事实,强烈支持将 Stathmin 作为预后标志物和新型抗肿瘤和抗转移治疗的靶点。