Tumour YAP1 and PTEN expression correlates with tumour-associated myeloid suppressor cell expansion and reduced survival in colorectal cancer

Abstract

The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33+ MDSC number and Yes-associated protein 1 (YAP1) and phosphatase and tensin homologue (PTEN) levels in CRC patients (P < 0·05). Moreover, the CD33+ MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0·05). Notably, CD33+ MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC-derived cell lines were associated with CRC-derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC-derived MDSC induction. A mechanistic analysis revealed that YAP1 promoted CRC-derived MDSC induction by suppressing PTEN expression to up-regulate COX-2, P-AKT and P-p65 in CRC-derived cells, leading to secretion of the cytokine granulocyte–macrophage colony-stimulating factor. Our findings establish a novel mechanism of pro-tumorigenic MDSC induction mediated by ectopic YAP1 and PTEN expression in CRC.