Dataset Information

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

ABSTRACT: Epithelial-mesenchymal transition (EMT)-induced metastasis contributes to human colorectal cancer (CRC) progression, especially in advanced CRC. However, the underlying mechanism of ?-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 ?-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 ?-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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6030168 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhang Yue Y Li Aimin A Shi Jiaolong J Fang Yuxin Y Gu Chuncai C Cai Jianqun J Lin Chuang C Zhao Liang L Liu Side S

Cell death & disease 20180703 7

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 sup ...[more]

PMID: 29970879

Similar Datasets

Project description:BackgroundResistance of colorectal cancer (CRC) cells to radiotherapy considerably contributes to poor clinical outcomes of CRC patients. Microarray profiling in this study revealed the differentially expressed forkhead box Q1 (FOXQ1) in CRC, and thus we aimed to illustrate the role of FOXQ1 in CRC by modulating stemness and radio-resistance of CRC cells.MethodsCRC and adjacent normal tissues were collected from CRC patients, and the correlation between FOXQ1 expression and CRC prognosis was analyzed. Subsequently, we determined the expression of FOXQ1, sirtuin 1 (SIRT1) and β-catenin in CRC tissues and cell lines. The binding affinity between FOXQ1 and SIRT1 and that between SIRT1 and β-catenin were validated with luciferase reporter gene, Co-IP and ChIP assays. Following a metagenomics analysis of CRC intestinal microbiota, the effects of the FOXQ1/SIRT1/β-catenin axis on CRC stem cell phenotypes and radio-resistance was evaluated in vitro and in vivo through manipulation of gene expression. Besides, mouse feces were collected to examine changes in intestinal microbiota.ResultsFOXQ1 was highly expressed in CRC tissues and cells and positively correlated with poor prognosis of CRC patients. FOXQ1 overexpression contributed to resistance of CRC cells to radiation. Knockdown of FOXQ1 inhibited the stemness of CRC cells and reversed their radio-resistance. FOXQ1 enhanced the transcriptional expression of SIRT1, and SIRT1 enhanced the expression and nuclear translocation of β-catenin. Knockdown of FOXQ1 repressed SIRT1 expression, thus reducing the stemness and radio-resistance of CRC cells. Moreover, FOXQ1 knockdown suppressed CRC xenograft formation in xenograft-bearing nude mice through inhibiting SIRT1 and β-catenin to reduce the content of pathological bacteria that were up-regulated in CRC.ConclusionFOXQ1-mediated SIRT1 upregulation augments expression and nuclear translocation of β-catenin and benefits CRC-related intestinal pathological bacterial, thereby enhancing the stemness and radio-resistance of CRC cells.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets