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.
Highlights
Colon cancer (CC) is the sixth most common cancer type and the fifth leading cause of cancer-related deaths in China [1]
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
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
Summary
Colon cancer (CC) is the sixth most common cancer type and the fifth leading cause of cancer-related deaths in China [1]. Since dietary characteristics have changed in recent years, the mortality of colon cancer has been estimated 608,000 people each year in the world [2]. The incidence of CC is increasing faster in recent years with estimated 274,841 cases and the mortality of that is 132,110 cases accounted for 48% of all the CC cases in China [1]. Diagnosis and development of surgical resection, radiation therapy, chemotherapy and immunotherapy for CC, the survival rates of CC patients were almost not improved during the past decade. The CC patients with metastasis have even lower survival rate compared with the patients in the absent of metastasis. Many studies investigated whether there are any possible genes that associate with prognosis and tumorigenesis of CC, and WNT1 inducible signalling pathway protein 1, WISP1, has emerged as possible markers for human diseases including injuries and cancers [3]
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