title: ART1 promotes starvation-induced autophagy: a possible protective role in the development of colon carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath Bath, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Threadgill
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Faculty of Basic Medical Science, Chongqing Medical University Chongqing, China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Mou
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Guang-Lin
authors.initials: GL
authors.lastname: Song
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kuang
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Faculty of Basic Medical Science, Chongqing Medical University Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Clinical Medical College, Chongqing Medical University Chongqing, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Gao
authors.affiliation: Clinical Medical College, Chongqing Medical University Chongqing, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Clinical Medical College, Chongqing Medical University Chongqing, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Meng
keywords: ART1; Autophagy; apoptosis; colon carcinoma; proliferation