IDDF2019-ABS-0341 HomeoboxC6 promotes metastasis of colorectal cancer by activating Wnt/b-catenin and inducing EMT

Background HomeoboxC6 (HOXC6) belongs to the homeobox family, members of which encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. It was found to be upregulated in multiple-cancers, such as breast cancer, prostate cancer, liver cancer, colorectal cancer and so on. Upregulation of HOXC6 also contributed to poor prognosis in colorectal cancer. However, there were very few researches about HOXC6 in colorectal cancer and it was still unknown how it plays its role in tumor cell proliferation and metastasis in colorectal cancer. Methods Cell culture and HOXC6 overexpressed HCT116 cell line constructionHCT116 was cultured with 1640 medium added with 10% FBS and 1% Penicillin-Streptomycin Solution with general culture condition. Clinical patient tumor samples7 patients including 4 left-sided patients and 3 right-sided colorectal patients were collected for HOXC6 expression analysis compared to their para-tumor samples Total protein and plasma & nuclear protein extraction and Western blot analysis CCK8 and transwell with or without matrigel analysis RNASeq and Co-IP analysis Total mRNA extraction and qPCR analysis Survival analysis of gene expression in UALCAN database Results HOXC6 was upregulated in right-sided colorectal cancer (figure 1A) Upregulation of HOXC6 contributed to migration and invasion but not in proliferation (figure 1D, E) Wnt/b-catenin and P53 pathway were activated by HOXC6 upregulation (figure 1F, G, H) DKK1 was upregulated by HOXC6 and could combined to HOXC6 (figure 1I) EMT was induced by HOXC6 upregulation (figure 1J) Upregulation of HOXC6 contributed to poor prognosis in colorectal cancer (figure 1K) Conclusions HOXC6 could upregulate DKK1, Wnt/b-catenin pathways and induce EMT which contributed to metastasis in colorectal cancer. Further, we will explore the mechanisms of how upregulation of DKK1 could activate Wnt/b-catenin pathway.