The interaction between S100A2 and KPNA2mediates NFYA nuclear import and is a novel therapeutic target for colorectal cancermetastasis

Abstract

Nucleocytoplasmic transport of proteins isdisrupted and dysregulated in cancer cells. Nuclear pore complexes and cargoproteins are two main transportation regulators. However, the mechanismregulating nucleocytoplasmic transport in cancer remains elusive. Here, weidentifified a S100A2/KPNA2 cotransport complex that transports thetumor-associated transcription factor NFYA in colorectal cancer (CRC). Throughthe S100A2/KNPA2 complex, depending on its interaction with S100A2, NFYA istransported to the nucleus and inhibits the transcriptional activity ofE-cadherin, which in turn promotes CRC metastasis. Targeting the S100A2/KPNA2binding sites with the specifific inhibitor delanzomib is a potentialtherapeutic approach for CRC.