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ACLY facilitates colon cancer cell metastasis by CTNNB1
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740040/ https://www.ncbi.nlm.nih.gov/pubmed/31511060 http://dx.doi.org/10.1186/s13046-019-1391-9 |
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author | Wen, Jun Min, Xuejie Shen, Mengqin Hua, Qian Han, Yuan Zhao, Li Liu, Liu Huang, Gang Liu, Jianjun Zhao, Xiaoping |
author_facet | Wen, Jun Min, Xuejie Shen, Mengqin Hua, Qian Han, Yuan Zhao, Li Liu, Liu Huang, Gang Liu, Jianjun Zhao, Xiaoping |
author_sort | Wen, Jun |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1391-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6740040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67400402019-09-16 ACLY facilitates colon cancer cell metastasis by CTNNB1 Wen, Jun Min, Xuejie Shen, Mengqin Hua, Qian Han, Yuan Zhao, Li Liu, Liu Huang, Gang Liu, Jianjun Zhao, Xiaoping J Exp Clin Cancer Res Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1391-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-09-12 /pmc/articles/PMC6740040/ /pubmed/31511060 http://dx.doi.org/10.1186/s13046-019-1391-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Wen, Jun Min, Xuejie Shen, Mengqin Hua, Qian Han, Yuan Zhao, Li Liu, Liu Huang, Gang Liu, Jianjun Zhao, Xiaoping ACLY facilitates colon cancer cell metastasis by CTNNB1 |
title | ACLY facilitates colon cancer cell metastasis by CTNNB1 |
title_full | ACLY facilitates colon cancer cell metastasis by CTNNB1 |
title_fullStr | ACLY facilitates colon cancer cell metastasis by CTNNB1 |
title_full_unstemmed | ACLY facilitates colon cancer cell metastasis by CTNNB1 |
title_short | ACLY facilitates colon cancer cell metastasis by CTNNB1 |
title_sort | acly facilitates colon cancer cell metastasis by ctnnb1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740040/ https://www.ncbi.nlm.nih.gov/pubmed/31511060 http://dx.doi.org/10.1186/s13046-019-1391-9 |
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