LYPD8 regulates the proliferation and migration of colorectal cancer cells through inhibiting the secretion of IL-6 and TNF-α

Ly6/Plaur domain-containing 8 (LYPD8) contributes to the segregation of intestinal microbiota and intestinal epithelia and is critical for the prevention of intestinal inflammation. However, its relevance in cancer biology remains to be fully elucidated. The present study aimed to clarify the biological effects of LYPD8 on colon cancer tissue from patients and colorectal cancer (CRC) cells. The results revealed that the expression of LYPD8 was significantly reduced in the CRC tissue compared with that in precancerous tissue and normal tissue, particularly in stage III tissue. The results also revealed increased levels of P65 and signal transducer and activator of transcription 3 (STAT3) phosphorylation and increased secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in CRC tissue compared with levels in precancerous tissue. Supporting these findings, the levels of secreted TNF-alpha and IL-6 were significantly reduced when LYPD8 was overexpressed in human CRC cells, and the secretion of TNF-alpha and IL-6 were positively associated with the phosphorylation of STAT3 and P65. However, this trend was restored upon supplementation with TNF-alpha and IL-6 in CRC cells. Furthermore, the overexpression of LYPD8 in CRC cells significantly inhibited CRC cell proliferation and migration. Overall, the LYPD8-mediated tumor-inhibiting role involves a direct effect on the secretion of IL-6/TNF-alpha in CRC cells by reducing the phosphorylation of STAT3 and P65.