Autophagy plays a protective role in
colorectal carcinoma.
Arginine ADP-ribosyltransferase 1 (ART1) is an important
mono-ADP-ribose transferase, which has been shown to play a role in biological processes such as proliferation and invasion of
cancer cells. Interestingly, the role of ART1 in the regulation of autophagy is still not clear. We examined effects of overexpression or knockdown of ART1 by lentiviral transfection on
starvation-induced autophagy of colon
carcinoma CT26 cell lines in vivo and in vitro. The formation of autophagosome was detected by electron microscopy,
acridine orange staining and expression of LC3 B. The molecular contributions of ART1 in regulation of autophagy were detected by western blotting or by co-immunoprecipitation. Additionally, inhibitors were used to study further the signaling pathway of ART1 in the regulation of autophagy. CCK8 assay, plate cloning assay, soft
agar assay, examination of subcutaneous transplanted
carcinoma in BALB/c mice, flow cytometry and
Hoechst33342 staining were used to assess survival and apoptotic ability when
starvation-induced autophagy modulated by ART1 was inhibited by 3-MA. Overexpression of ART1 promoted
starvation-induced autophagy, which related to increases in the expression of Rac1, NF-κB, PARP-1, LKB1 and p-AMPK and a decrease in the expression of p-P70S6K. Correspondingly, knockdown of ART1 caused the opposite effects. ART1 also interacted with
integrin α7. Additionally, changes of
protein expressions were further validated following inhibition of Rac1 and PARP-1 in the
starvation-induced ART1-GFP CT26 cells. Inhibition of ART1-stimulated
starvation-induced autophagy restrained the growth and promoted apoptosis. ART1 is thus relevant in
starvation-induced autophagy in
colorectal carcinoma and may play essential roles in therapeutic anticancer strategies.