Endoplasmic reticulum stressed promotes colorectal cancer cell proliferation and invasion through ATG5-mediated autophagy pathway
10.3760/cma.j.cn.115807-20220225-00046
- VernacularTitle:内质网应激通过ATG5介导的自噬通路促进结直肠癌细胞增殖和侵袭
- Author:
Hong PENG
1
;
Juan LIU
;
Ziwei WANG
;
Shigui HUANG
;
Mingsha PENG
;
Lei GONG
;
Xueya FENG
Author Information
1. 南充市中心医院，川北医学院第二临床医学院肛肠外科，南充 637000，
- Keywords:
Colorectal cancer;
Endoplasmic reticulum stressed;
Autophagy;
Proliferation;
Invasion
- From:
Chinese Journal of Endocrine Surgery
2022;16(5):616-621
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of endoplasmic reticulum stressed (ER) on colorectal cancer (CRC) cell proliferation and invasion via ATG5-mediated autophagy pathway and the underlying mechanism.Methods:We performed bioinformatics analysis to identify the expression level of PERK, ATF6 and ATG5 in CRC tissues and adjacent tissues and the correlation between PERK and ATG5 expression in CRC tissues.The expression level of PERK in CRC cell lines was examined by qRT-PCR assay. Cell proliferation was quantified by CCK-8.The invasion of the cells was detected by Transwell.Western blot assay was performed to verify the levels of protein. The levels of autophagy were examined by electron microscopy.Results:PERK and ATF6 expression in CRC tissues was higher than that in the adjacent tissues and PERK expression was higher in CRC cells than intestinal mucosal cells. Expression level of PERK in CRC cell lines HCT116,SW480,HT29,LoVo and colonic mucosa cell lines FHC was 1.51±0.04,3.12±0.05,2.19±0.04,2.38±0.06 and 0.98±0.04 ( P<0.001) .The increased expression of PERK promoted CRC cell proliferation and invasion. PERK expression levels was positively associated with ATG5 expression levels ( r=0.52, P<0.001) and overexpression of PERK accelerated the protein expression of ATG5 (1.00±0.04,3.53±0.07, t=74.61, P<0.001) . ATG5 was highly expressed in CRC tissues. Overexpression of ATG5 could promote proliferation,invasion and accelerate autophagy of CRC cells (the number of autophagosomes in the blank control group,the negative control group and ATG5-Overexpression group was 4.33±1.53, 4.00±1.00, 9.67±2.52, and t=3.14,3.62, P=0.035,0.022, respectively) .ATG5 promoted colorectal cancer cell proliferation and invasion through autophagy pathway. Conclusion:ER stressed-CRC cells could promote CRC cell proliferation and invasion through ATG5-mediated autophagy pathway.
