FAT1 inhibits cell proliferation of esophageal squamous cell carcinoma through regulating the expression of CDK4/CDK6/CCND1 complex
10.3760/cma.j.issn.0253-3766.2018.01.003
- VernacularTitle: FAT1通过调节CDK4/CDK6/CCND1复合物表达抑制食管鳞癌细胞增殖
- Author:
Xiaoling HU
1
,
2
;
Yuanfang ZHAI
3
;
Guodong LI
4
;
Jianfeng XING
5
;
Jie YANG
3
;
Yanghui BI
3
;
Juan WANG
3
;
Ruyi SHI
3
Author Information
1. Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China
2. Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, China
3. Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, China
4. Department of Otorhinolaryngology, Shanxi Provincial People′s Hospital, Taiyuan 030012, China
5. Function Laboratory, Shanxi Medical University, Taiyuan 030001, China
- Publication Type:Journal Article
- Keywords:
Esophageal neoplasms;
Carcinoma, squamous cell;
FAT1;
Cell proliferation;
Cell cycle
- From:
Chinese Journal of Oncology
2018;40(1):14-20
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the expression of FAT1 in esophageal squamous cell carcinoma (ESCC) tissues, and its effect on cell proliferation.
Methods:The expression levels of FAT1 protein in human ESCC tissues and matched adjacent normal tissues were determined by immunohistochemistry (IHC). Lentivirus based knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assays was performed to examine the effect of FAT1 on the proliferation of these ESCC cells. Colony formation assay was used to detect the colony formation ability. Flow cytometry was performed to analyze the cell cycle and apoptosis. The expression levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR) and Western blot.
Results:The relative expression of FAT1 in ESCC tissues was 66.97±21.53, significantly lower than 78.13±16.76 of adjacent normal tissues(P<0.05). Knockdown of FAT1 promoted cell proliferation and colony formation. In YSE2 cell, the division time in negative control (NC) group was (1 570±51) min, significantly longer than (1 356±31) min in shFAT1 group. In Colo680N cell, division time in NC group was (1 532±53) min, significantly longer than (1 290±30) min in shFAT1 group (P<0.05). Knockdown of FAT1 promoted G1-to S-phase transition and resulted in the upregulation of CDK4/CDK6/CCND1.
Conclusion:FAT1 inhibits the proliferation and G1-to S-phase transition of ESCC cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.
