Cancer Res:抗癌细胞转移分子Liminib

法国国家科研中心28日发表公报说，法国、澳大利亚和英国研究人员发现一种新的分子，不仅可以遏制癌细胞增殖，还能抑制其流动性，防止癌细胞转移。

恶性肿瘤细胞对化疗产生抗药性是导致传统化疗失败的一个重要因素，癌细胞转移也是造成患者死亡最普遍的原因。鉴于此，由法、澳、英三国研究人员组成的团队近十年来一直在寻找新的有效药物，阻止癌细胞转移形成新的病灶。

研究人员通过一个高通量自动化筛选平台对近3万种分子进行筛选，希望能找到具有抗癌性和抗转移性的分子。最终，他们在法国居里研究所的分子库里找到了一种名为Liminib的分子，这种分子对LIM激酶具有抑制作用。而LIM激酶能够调节细胞骨架的活性，在癌细胞的侵袭和转移过程中发挥重要作用。

据称，Liminib分子是目前发现的首种LIM激酶抑制剂，它和目前广泛使用的抗癌药物紫杉醇作用机制不同，是通过破坏肌动蛋白的细胞骨架来阻止癌细胞扩散和转移。对小鼠模型的实验也表明，它对多种癌细胞具有杀伤力。

研究人员认为，人们有望在将来利用这种分子开发出新的癌症治疗方法。相关研究成果已经发表在《癌症研究》杂志上。（生物谷Bioon.com）

doi: 10.1158/0008-5472.CAN-11-3342

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Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Renaud Prudent, Emilie Vassal-Stermann, Chi-Hung Nguyen, Catherine Pillet, Anne Martinez, Chloé Prunier, Caroline Barette, Emmanuelle Soleilhac, Odile Filhol, Anne Beghin, Glaucio Valdameri, Stéphane Honoré, Samia Aci-Sèche, David Grierson, Juliana Antonipillai, Rong Li, Attilio Di Pietro, Charles Dumontet, Diane Braguer, Jean-Claude Florent, Stefan Knapp, Ora Bernard and Laurence Lafanechère

The emergence of tumor resistance to conventional microtubule-targeting drugs restricts their clinical use. Using a cell-based assay that recognizes microtubule polymerization status to screen for chemicals that interact with regulators of microtubule dynamics, we identified Pyr1, a cell permeable inhibitor of LIM kinase, which is the enzyme that phosphorylates and inactivates the actin-depolymerizing factor cofilin. Pyr1 reversibly stabilized microtubules, blocked actin microfilament dynamics, inhibited cell motility in vitro and showed anticancer properties in vivo, in the absence of major side effects. Pyr1 inhibition of LIM kinase caused a microtubule-stabilizing effect, which was independent of any direct effects on the actin cytoskeleton. In addition, Pyr1 retained its activity in multidrug-resistant cancer cells that were resistant to conventional microtubule-targeting agents. Our findings suggest that LIM kinase functions as a signaling node that controls both actin and microtubule dynamics. LIM kinase may therefore represent a targetable enzyme for cancer treatment.

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