2. Academic Validation
  3. Imbalanced LIMK1 and LIMK2 expression leads to human colorectal cancer progression and metastasis via promoting β-catenin nuclear translocation

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

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.

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