Mast cells (MCs), a type of granulocytic immune cell, can either support or inhibit colorectal cancer (CRC) progression. This duality may result from subtype-specific interactions between MCs and CRC cells. Notably, BRAF-mutant CRCs are enriched in intestinal secretory cell populations. Our study reveals that MCs are particularly abundant in BRAF-mutant CRC, likely attracted by factors secreted by these tumor-associated secretory cells. Using direct coculture experiments, we found that MCs induce epithelial-to-mesenchymal transition (EMT) in CRC cells, requiring both physical contact and calcium signaling. Disrupting LFA-1/ICAM1 integrin binding attenuated EMT-associated marker expression triggered by coculture. Moreover, MCs can transfer biomolecules, including mRNA, to CRC cells during these interactions. This research highlights a previously unreported contact-dependent pro-tumor role of MCs in CRC and demonstrates intercellular molecular transfer, suggesting that targeting MC–CRC interactions, especially through integrin pathways, may offer novel therapeutic strategies for aggressive CRC variants.
