Abstract
BackgroundThe roles played by cholesterol in cancer development and progression represent a popular field in the cancer community. High cholesterol levels are positively correlated with the risk of various types of cancer. APOA-I binding protein (AIBP) promotes the reverse cholesterol transport pathway (RCT) in cooperation with Apolipoprotein A-I (APOA-I) or high-density lipoprotein cholesterol. However, the combined effect of AIBP and APOA-I on intestinal tumor cells is still unclear.MethodsImmunohistochemistry, western blot and qPCR were performed to investigate the expression of AIBP and APOA-I in intestinal tumor tissues and cell lines. The anti-tumor activity of AIBP and APOA-I was evaluated by overexpression or recombinant protein treatment. Cholesterol efflux and localization of lipid raft-related proteins were analyzed by a cholesterol efflux assay and lipid raft fraction assay, respectively.ResultsHere, we reported that both AIBP expression and APOA-I expression were associated with the degree of malignancy in intestinal tumors. Co-overexpression of AIBP and APOA-I more potently inhibited colon cancer cell-mediated tumor growth and metastasis compared to overexpression of each protein individually. Additionally, the recombinant fusion proteins of AIBP and APOA-I exhibited a significant therapeutic effect on tumor growth in Apcmin/+ mice as an inherited intestinal tumor model. The synergistic effect of the two proteins inhibited colon cancer cell migration, invasion and tumor-induced angiogenesis by promoting cholesterol efflux, reducing the membrane raft content, and eventually disrupting the proper localization of migration- and invasion-related proteins on the membrane raft. Moreover, cyclosporine A, a cholesterol efflux inhibitor, rescued the inhibitory effect induced by the combination of AIBP and APOA-I.ConclusionsThese results indicate that the combination of APOA-I and AIBP has an obvious anticancer effect on colorectal cancer by promoting cholesterol efflux.
Highlights
The roles played by cholesterol in cancer development and progression represent a popular field in the cancer community
Apolipoprotein A-I (APOA-I) binding protein (AIBP) expression and APOA‐I expression are associated with the malignant degree of intestinal tumors APOA-I is synthesized predominantly in the liver and small intestine [9], and AIBP is reportedly ubiquitously expressed in various organs [13], but their expression in malignant conditions of the gastrointestinal tract remains unknown
We examined AIBP or APOA-I expression in normal intestinal epithelial tissues, adenomas, and large tumors (Apcmin/+ mice ranging in age from 200 to 230 days) [22, 23]
Summary
The roles played by cholesterol in cancer development and progression represent a popular field in the cancer community. APOA-I binding protein (AIBP) promotes the reverse cholesterol transport pathway (RCT) in cooperation with Apolipoprotein A-I (APOA-I) or high-density lipoprotein cholesterol. As cholesterol-enriched plasma membranes, play an active role in the regulation of cell proliferation, apoptosis, migration and invasion, which are important biological processes involved in cancer initiation, development and progression [6,7,8]. AIBP was reported to cooperate with HDL to reduce the lipid raft content of endothelial cells by accelerating cholesterol efflux, leading to restriction of cell migration and angiogenesis in vivo and in vitro [13, 14]. AIBP promoted APOA-I binding to ATP-binding cassette transporter member 1 (ABCA1) on the cell membranes of macrophages to enhance cholesterol efflux, prevented lipid accumulation and reduced foam cell formation [15]. We hypothesized that this synergy affects intestinal epithelial tumor development and cancer cells’ biological behavior
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
