Poster Presentation 32nd Lorne Cancer 2020

Exosomes containing oncogenic mutant β-catenin activate Wnt signaling pathway in the recipient cells (#156)

Pamali Fonseka 1 , Suresh Mathivanan 1
  1. La Trobe University, Bundoora, VIC, Australia

Mutations in β-catenin, especially at the residues critical for its degradation, renders it constitutively active. Here, we show that mutant β-catenin can be transported via exosomes and activate Wnt signaling pathway in the recipient cells. An integrative proteogenomic analysis identified the presence of mutated β-catenin in exosomes secreted by colorectal cancer (CRC) cells. Follow up experiments established that exosomes released from LIM1215 CRC cells stimulated Wnt signaling pathway in the recipient cells with wild type β-catenin. SILAC-based quantitative proteomics analysis confirmed the transfer of mutant β-catenin to the nucleus of the recipient (RKO CRC) cells. In vivo tracking of DiR labelled exosomes in mouse implanted with RKO CRC cells revealed its bio distribution, confirmed the activation of Wnt signaling pathway in tumor cells and increased the tumor burden. Overall, for the first time, this study reveals that exosomes can transfer mutant β-catenin to the recipient cells and promote cancer progression.