Affiliations 

  • 1 Faculty of Science and Engineering, University of Nottingham Malaysia, 43500 Semenyih, Selangor, Malaysia. Electronic address: khyy5czx@nottingham.edu.my
  • 2 Faculty of Science and Engineering, University of Nottingham Malaysia, 43500 Semenyih, Selangor, Malaysia. Electronic address: WanYong.Ho@nottingham.edu.my
  • 3 China-ASEAN College of Marine Sciences, Xiamen University Malaysia, 43900 Sepang, Selangor, Malaysia. Electronic address: skyeap@xmu.edu.my
Life Sci, 2024 Jun 15;347:122609.
PMID: 38580197 DOI: 10.1016/j.lfs.2024.122609

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.