High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis

Abstract

Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher levels of WISP1. Downregulation of WISP1 inhibited cell proliferation and invasion through increasing apoptosis and blocking cell cycle at G1 phase in CC LOVO and RKO cells. Besides, Gene set enrichment analysis (GSEA) revealed that relative genes involved in the Cell adhesion molecules and Cytokine-cytokine receptor interaction pathways were enriched in WISP1-higher expression patients. Western blot analysis showed that Cell adhesion molecules pathway associated genes (ICAM- 1, VCAM-1, SDC2 and CDH2) and Cytokine-cytokine receptor interaction pathway associated genes (VEGFC, CCL18, CXCR4 and TGFBR1) were also modulated by WISP1 downregulation. Then, we found that the protein β-catenin was identified as a binding partner of WISP1 and mediated the functions of WISP1 through promoting cell proliferation and invasion in LOVO and RKO cells. Further in vivo tumor formation study in nude mice indicated that inhibition of WISP1 delayed the progress of tumor formation and inhibited PCNA expression. These results indicate that WISP1 could act as an oncogene and may serve as a promising therapeutic strategy for colon cancer.

The tumor cell‐secreted matricellular protein WISP 1 drives pro‐metastatic collagen linearization

“…Furthermore, in the clinic, WISP1 expression levels are generally higher in tumors than in normal tissues (Gurbuz & Chiquet-Ehrismann, 2015) and high WISP1 levels in primary tumors correlate with shorter periods of distant metastasisfree survival in a number of cancers, including breast, gastric, ovarian, colorectal, and oral squamous cell carcinomas (Clausen et al, 2016;Wu et al, 2016). In support of this idea, our data indicate that knockdown of Wisp1 in tumor cells prevents collagen linearization and inhibits metastasis.…”

“…A correlation between high WISP1 expression and shorter distant metastasis-free survival was also observed for patients with luminal A breast cancers (Fig 5D), whereas no correlation was found for patients with luminal B breast cancer subtype ( Fig 5E). Furthermore, high levels of WISP1 also associate with faster disease progression and poor prognosis of other cancer types, such as gastric (Fig 5F), ovarian (Fig 5G), and colorectal cancer (Wu et al, 2016), as well as oral squamous cell carcinoma (Clausen et al, 2016). Furthermore, high levels of WISP1 also associate with faster disease progression and poor prognosis of other cancer types, such as gastric (Fig 5F), ovarian (Fig 5G), and colorectal cancer (Wu et al, 2016), as well as oral squamous cell carcinoma (Clausen et al, 2016).…”

“…The EMBO Journal 38: e101302 | 2019 ª 2019 The Authors progression and poor prognosis of other cancer types, such as gastric ( Fig 5F), ovarian ( Fig 5G), and colorectal cancer (Wu et al, 2016), as well as oral squamous cell carcinoma (Clausen et al, 2016). Therefore, WISP1 might contribute to collagen linearization and metastatic progression in many cancers.…”

The role of CCN4/WISP-1 in the cancerous phenotype

“…Therefore, in a report published in 2016, Wu et al took a fresh look at the issue 30. They found that higher levels of CCN4 expression in human colon cancer cases were associated with a poor prognosis.…”

Talin-1 interaction network promotes hepatocellular carcinoma progression

“…Multiple studies have reported that WISP1 can stimulate cell adhesion [30, 31]. In addition, both WISP1 and MUC1 were reported to promote cell adhesion via activating EMT process.…”