Downregulation of cytokeratin 18 increases NMIIA expression and promotes breast cancer metastasis
- Author:
Rui-Zan SHI
1
;
Ya-Nan NIU
1
;
Yu GAO
1
;
Ke-Min LI
1
;
Rui-Han LI
1
;
Lin-Hong LIU
1
;
Min CHEN
1
;
Xuan-Ping ZHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: breast cancer; c-Abl-ERK signaling pathway; co- localization; cytokeratin 18; metastasis; non-muscle II A
- From: Chinese Pharmacological Bulletin 2022;38(6):861-865
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the role of aberrant cytokeratin 18(CK18) expression in breast cancer metastasis, anrl to elucidate the mechanism by identif¬ying its target.Methods The expression of CK.18 in human breast cancer tissues and cells was determined using immunohistochemical staining and Western blot, respectively.CK18 expression in human breast cancer MCF-7 cells was effectively down-regulated by shRNA, and its effect on breast cancer metastasis was further determined by scratch wound healing assay.The co-lo- cation of CK18 and non-muscle II A ( NMIIA) in MCF-7 cells was examined using double immunofluo¬rescence staining.The effect of CK18 down-regulation on the levels of NMIIA and c-Abl-ERK signaling was quantified by Western blot.Results Lower CK18 lev¬els was found in metastatic than that in primary breast cancer tissues and in highly invasive MDA-MB-231 than that in MCF-7 cells.CK.18 down-regulation pro¬moted the wound repair ability of MCF-7 cells 72h after scratch.CK18 and NMIIA were shown to co-locate in cytoplasm of MCF-7 cells.Moreover, down-regulation of CK18 increased NMIIA expression and activated the c-Abl-ERK signaling pathway in MCF-7 cells.Con¬clusions Down-regulation of CK18 could promote me¬tastasis of breast cancer, which is related to increased NMIIA expression and the activation of c-Abl-ERK sig¬naling pathway.
