Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy

Xiuyan Yang; Jie Zhong; Qiufen Zhang; Li Feng; Zhen Zheng; Jian Zhang; Shaoyong Lu

doi:10.3389/fmolb.2021.662579

Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy

Front Mol Biosci. 2021 Apr 22:8:662579. doi: 10.3389/fmolb.2021.662579. eCollection 2021.

Authors

Xiuyan Yang¹, Jie Zhong², Qiufen Zhang², Li Feng², Zhen Zheng², Jian Zhang^{1

2}, Shaoyong Lu¹

Affiliations

¹ Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

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.

Keywords: APC-Asef inhibitors; colorectal cancer therapy; peptide inhibitors; small molecule inhibitors; structure based drug design.

Publication types

Review