Nuclear HIC-5 in NFs was reported to induce LOX expression and was responsible for tumorigenesis in colorectal cancer.28 Nuclear HIC-5 also works as a stromal-specific coactivator of androgen receptor (AR) to regulate AR target genes in prostate tumors, which then creates a microenvironment conducive to tumor growth and progression.49 The nuclear accumulation of HIC-5 in NFs but not in CAFs may indicate that nuclear HIC-5 transduces signals and lays the foundation for early tumorigenesis, while cytoplasmic HIC-5 mainly contributes to cancer progression. This evidence concerns the gene LOX and colorectal cancer.