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Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy
In Colorectal cancer (CRC), adenomatous polyposis coli (APC) directly interacts with the Rho guanine nucleotide exchange factor 4 (Asef) and releases its GEF activity. Activated Asef promotes the aberrant migration and invasion of CRC cell through a CDC42-mediated pathway. Knockdown of either APC or...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100458/ https://www.ncbi.nlm.nih.gov/pubmed/33968990 http://dx.doi.org/10.3389/fmolb.2021.662579 |
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author | Yang, Xiuyan Zhong, Jie Zhang, Qiufen Feng, Li Zheng, Zhen Zhang, Jian Lu, Shaoyong |
author_facet | Yang, Xiuyan Zhong, Jie Zhang, Qiufen Feng, Li Zheng, Zhen Zhang, Jian Lu, Shaoyong |
author_sort | Yang, Xiuyan |
collection | PubMed |
description | In Colorectal cancer (CRC), adenomatous polyposis coli (APC) directly interacts with the Rho guanine nucleotide exchange factor 4 (Asef) and releases its GEF activity. Activated Asef promotes the aberrant migration and invasion of CRC cell through a CDC42-mediated pathway. Knockdown of either APC or Asef significantly decreases the migration of CRC cells. Therefore, disrupting the APC-Asef interaction is a promising strategy for the treatment of invasive CRC. With the growth of structural information, APC-Asef inhibitors have been designed, providing hope for CRC therapy. Here, we will review the APC-Asef interaction in cancer biology, the structural complex of APC-Asef, two generations of peptide inhibitors of APC-Asef, and small molecule inhibitors of APC-Asef, focusing on research articles over the past 30 years. We posit that these advances in the discovery of APC-Asef inhibitors establish the protein-protein interaction (PPI) as targetable and provide a framework for other PPI programs. |
format | Online Article Text |
id | pubmed-8100458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81004582021-05-07 Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy Yang, Xiuyan Zhong, Jie Zhang, Qiufen Feng, Li Zheng, Zhen Zhang, Jian Lu, Shaoyong Front Mol Biosci Molecular Biosciences In Colorectal cancer (CRC), adenomatous polyposis coli (APC) directly interacts with the Rho guanine nucleotide exchange factor 4 (Asef) and releases its GEF activity. Activated Asef promotes the aberrant migration and invasion of CRC cell through a CDC42-mediated pathway. Knockdown of either APC or Asef significantly decreases the migration of CRC cells. Therefore, disrupting the APC-Asef interaction is a promising strategy for the treatment of invasive CRC. With the growth of structural information, APC-Asef inhibitors have been designed, providing hope for CRC therapy. Here, we will review the APC-Asef interaction in cancer biology, the structural complex of APC-Asef, two generations of peptide inhibitors of APC-Asef, and small molecule inhibitors of APC-Asef, focusing on research articles over the past 30 years. We posit that these advances in the discovery of APC-Asef inhibitors establish the protein-protein interaction (PPI) as targetable and provide a framework for other PPI programs. Frontiers Media S.A. 2021-04-22 /pmc/articles/PMC8100458/ /pubmed/33968990 http://dx.doi.org/10.3389/fmolb.2021.662579 Text en Copyright © 2021 Yang, Zhong, Zhang, Feng, Zheng, Zhang and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Yang, Xiuyan Zhong, Jie Zhang, Qiufen Feng, Li Zheng, Zhen Zhang, Jian Lu, Shaoyong Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy |
title | Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy |
title_full | Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy |
title_fullStr | Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy |
title_full_unstemmed | Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy |
title_short | Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy |
title_sort | advances and insights of apc-asef inhibitors for metastatic colorectal cancer therapy |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100458/ https://www.ncbi.nlm.nih.gov/pubmed/33968990 http://dx.doi.org/10.3389/fmolb.2021.662579 |
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