LIM结构域激酶2(LIMK2)是调节肌动蛋白和细胞骨架重组的72kDa蛋白。一旦被其上游活化剂(ROCK1)磷酸化,LIMK2可以磷酸化cofilin以使其失活。这减轻了肌动蛋白上的杠杆应力并允许发生聚合。肌动蛋白重排在调节细胞周期进程中至关重要,凋亡,和移民。据报道,ROCK1/LIMK2/cofilin通路的失调与各种实体癌(如乳腺癌)的发展有关。肺,前列腺癌和液体癌,比如白血病。这篇综述旨在评估来自多个体外报道的发现,在体内,以及LIMK2在不同人类癌症中的潜在肿瘤调节作用的临床研究。选定文献的发现揭示了激活AKT,EGF,和TGF-β途径可以上调ROCK1/LIMK2/cofilin途径的活性。除了cofilin,LIMK2可以调节其他蛋白质的细胞水平,如TPPP1,以促进微管聚合。肿瘤抑制蛋白p53可以激活LIMK2b,LIMK2的剪接变体,以诱导细胞周期停滞并允许DNA修复在细胞进入细胞周期的下一阶段之前发生。此外,几种非编码RNA,如miR-135a和miR-939-5p,还可以表观遗传调节LIMK2的表达。由于LIMK2的表达在几种人类癌症中失调,测量LIMK2的组织表达可能有助于诊断癌症和预测患者预后。由于LIMK2可以在癌症发展中发挥促进肿瘤和抑制肿瘤的作用,应进行更多的调查,以仔细评估在癌症患者中引入LIMK2抑制剂是否可以减缓癌症进展而不造成临床损害.
LIM domains kinase 2 (LIMK2) is a 72 kDa protein that regulates actin and cytoskeleton reorganization. Once phosphorylated by its upstream activator (ROCK1), LIMK2 can phosphorylate
cofilin to inactivate it. This relieves the levering stress on actin and allows polymerization to occur. Actin rearrangement is essential in regulating cell cycle progression, apoptosis, and migration. Dysregulation of the ROCK1/LIMK2/
cofilin pathway has been reported to link to the development of various solid cancers such as breast, lung, and prostate cancer and liquid cancer like leukemia. This review aims to assess the findings from multiple reported in vitro, in vivo, and clinical studies on the potential tumour-regulatory role of LIMK2 in different human cancers. The findings of the selected literature unraveled that activated AKT, EGF, and TGF-β pathways can upregulate the activities of the ROCK1/LIMK2/
cofilin pathway. Besides
cofilin, LIMK2 can modulate the cellular levels of other proteins, such as TPPP1, to promote microtubule polymerization. The tumour suppressor protein p53 can transactivate LIMK2b, a splice variant of LIMK2, to induce cell cycle arrest and allow DNA repair to occur before the cell enters the next phase of the cell cycle. Additionally, several non-coding RNAs, such as miR-135a and miR-939-5p, could also epigenetically regulate the expression of LIMK2. Since the expression of LIMK2 is dysregulated in several human cancers, measuring the tissue expression of LIMK2 could potentially help diagnose cancer and predict patient prognosis. As LIMK2 could play tumour-promoting and tumour-inhibiting roles in cancer development, more investigation should be conducted to carefully evaluate whether introducing a LIMK2 inhibitor in cancer patients could slow cancer progression without posing clinical harms.