Frontiers in Molecular Biosciences (2021-04-01)

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

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

Journal volume & issue
Vol. 8


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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.