title: KNOCKDOWN OF CASEIN KINASE 1e INHIBITS CELL PROLIFERATION AND INVASION OF COLORECTAL CANCER CELLS VIA INHIBITION OF THE Wnt/β-CATENIN SIGNALING.
abstract: Deregulation of casein kinase 1 epsilon (CK1ε) is involved in the development of multiple pathological disorders such as cancer, however the function and molecular mechanism of CK1εin cancer are still unclear. In the present study, we aimed to investigate the role of CK1ε in human colorectal cancer (CRC). The expression of CK1ε was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to observe the effects of lentivirus-mediated CK1ε shRNA (Lv-shCK1ε) on cell proliferation and invasive potential by MTT and Transwell assays in CRC cell line (SW480). As a result, we found that the expression of CK1ε protein was significantly increased in CRC tissues compared with that in adjacent non-cancerous tissues (ANCT) (68.9% vs 42.2%, P=0.017) and was correlated with the Dukes staging and depth of invasion in CRC patients (P=0.012; P=0.015). Knockdown of CK1ε reduced cell proliferation and invasion of CRC cells followed by the downregulation of wnt3α, β-catenin, PCNA and MMP-9. In conclusion, our findings show that high expression of CK1ε is positively associated with the Dukes staging and depth of invasion in CRC patients, and knockdown of CK1ε suppresses the growth and invasion of CRC cells through inhibition of the wnt/β-catenin signaling, suggesting that CK1ε may serve as a promising therapeutic target for the treatment of CRC.
authors.affiliation: Institute of Pediatric Translational Medicine, Shanghai Childrens Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: L C
authors.initials: LC
authors.lastname: Ye
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Childrens Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Childrens Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Childrens Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Childrens Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: H-F
authors.initials: HF
authors.lastname: Hong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Childrens Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: L-S
authors.initials: LS
authors.lastname: Qiu
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000368:Aged; D048149:Casein Kinase 1 epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009367:Neoplasm Staging; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D048149:Casein Kinase 1 epsilon; D020780:Matrix Metalloproteinase 9