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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Metastasis | Research

ACLY facilitates colon cancer cell metastasis by CTNNB1

Authors: Jun Wen, Xuejie Min, Mengqin Shen, Qian Hua, Yuan Han, Li Zhao, Liu Liu, Gang Huang, Jianjun Liu, Xiaoping Zhao

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstract

Background

Colon cancer is the second leading cancer worldwide. Recurrent disease and chemotherapeutic drug resistance are very common in the advanced stage of colon cancer. ATP-citrate lyase (ACLY), the first-step rate-controlling enzyme in lipid synthesis, is elevated in colon cancer. However, it remains unclear about the exact role of ACLY in the development of colon cancer metastasis.

Methods

To evaluate the role of ACLY in colon cancer metastasis, we performed cell migration and invasion assays in two ACLY-deficient colon cancer cell lines. Colon cancer mouse model is used to examine ACLY’s effects on colon metastasis potentials in vivo. We analyzed the correlation between ACLY and CTNNB1 protein in 78 colon cancer patients by Pearson correlation. To finally explore the relationship of ACLY and CTNNB1, we used western blots, migration and invasion assays to confirm that ACLY may regulate metastasis by CTNNB1.

Results

Our data showed that the abilities of cell migration and invasion were attenuated in ACLY-deficient HCT116 and RKO cell lines. Furthermore, we describe the mechanism of ACLY in promoting colon cancer metastasis in vitro and in vivo. ACLY could stabilize CTNNB1 (beta-catenin 1) protein by interacting, and the complex might promote CTNNB1 translocation through cytoplasm to nucleus, subsequently promote the CTNNB1 transcriptional activity and migration and invasion abilities of colon cancer cells. Immunohistochemical analysis of 78 colon cancer patients showed that the high expression levels of ACLY and CTNNB1 protein was positively correlated with metastasis of colon cancer.

Conclusions

These results shed new light on the molecular mechanism underlying colon cancer metastasis, which might help in improving therapeutic efficacy.
Appendix
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Metadata
Title
ACLY facilitates colon cancer cell metastasis by CTNNB1
Authors
Jun Wen
Xuejie Min
Mengqin Shen
Qian Hua
Yuan Han
Li Zhao
Liu Liu
Gang Huang
Jianjun Liu
Xiaoping Zhao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1391-9

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