Imbalanced LIMK1 and LIMK2 expression leads to human colorectal cancer progression and metastasis via promoting β-catenin nuclear translocation

  • Cell Death Dis. 2018 Jul 3;9(7):749. doi: 10.1038/s41419-018-0766-8.
Yue Zhang  1 ,  Aimin Li  1 ,  Jiaolong Shi  2 ,  Yuxin Fang  1 ,  Chuncai Gu  1 ,  Jianqun Cai  1 ,  Chuang Lin  3 ,  Liang Zhao  4 ,  Side Liu  5
Affiliations
  • 1. Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 2. Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, Guandong, China.
  • 3. Department of pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guandong, China.
  • 4. Department of pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guandong, China. [email protected].
  • 5. Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. [email protected].
PMID: 29970879 DOI: 10.1038/s41419-018-0766-8
Abstract

Epithelial-mesenchymal transition (EMT)-induced metastasis contributes to human colorectal Cancer (CRC) progression, especially in advanced CRC. However, the underlying mechanism of β-catenin in this process is elusive. We identified that LIM domain kinase (LIMK)2 was progressively downregulated with tumor progression from precancerous lesions to advanced Cancer. Gain- and loss-of-function assays revealed that LIMK2 inhibits cell proliferation via cell cycle arrest at the G1-S transition and suppresses the ability of cell metastasis by restricting the EMT process. Reduced LIMK2 expression enhanced the nuclear accumulation of β-catenin and activated the Wnt signaling pathway, thus contributing to tumor progression. A homolog of the LIMK family, LIMK1, which was overexpressed throughout tumor progression, served as a competitive inhibitor of LIMK2 via β-catenin nuclear translocation. The imbalanced expression of LIMK1 and LIMK2 is important in CRC progression, and the combined effects provide a new insight into the mechanism of CRC progression. These findings provide a new understanding for LIMK-based Anticancer therapy.