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

Abstract

Summary 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.