The invention relates to application of IGFBP7 in
clinical diagnosis of
colorectal cancer and application of IGFBP7 as a
drug target. The research shows that the expression quantity of IGFBP7 secreted by tumor endothelial cells is continuously reduced in the
colorectal tumor formation process related to
inflammation.
Functional analysis proves that the endothelial-derived IGFBP7 is secreted into a
tumor microenvironment and plays a role in resisting
angiogenesis. In addition, the CRC cells can actively ingest the vesicles containing the IGFBP7. The IGFBP7 reduces the activity of a TGF-beta1
signal channel by inhibiting the expression of EGR1, thereby inhibiting the proliferation and migration of
tumor cells. What is worthy of attention is that VAPA (
Vesicle-associated
Membrane Protein Associated
Protein A) is identified to be a key factor for mediating IGFBP7 vesicles to be transferred to
lysosome, and VAPA promotes the degradation of IGFBP7, so that the
cancer suppression function of the IGFBP7 is weakened. The endothelial
cell-derived IGFBP7 inhibits the progress of CRC (
cyclic redundancy check) through an EGR1 / TGF-beta 1 pathway, and VAPA-mediated
lysosome degradation limits the
cancer inhibition effect of the endothelial
cell-derived IGFBP7. The discovery emphasizes that the endothelial
cell-derived IGFBP7 is a promising therapeutic target in the field of
colorectal cancer.