Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma.
10.1186/s40880-018-0267-2
- Author:
Yan LIU
1
;
Xiaojie TAN
1
;
Wenbin LIU
1
;
Xi CHEN
1
;
Xiaomei HOU
1
;
Dan SHEN
2
;
Yibo DING
1
;
Jianhua YIN
1
;
Ling WANG
1
;
Hongwei ZHANG
1
;
Yongwei YU
3
;
Jianguo HOU
2
;
Timothy C THOMPSON
4
;
Guangwen CAO
5
Author Information
1. Department of Epidemiology, Second Military Medical University, Shanghai, 200433, P. R. China.
2. Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
3. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
4. Genitourinary Medical Oncology-Research, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
5. Department of Epidemiology, Second Military Medical University, Shanghai, 200433, P. R. China. gcao@smmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Clear cell renal cell carcinoma;
Follistatin-like protein 1;
HIF-2α;
NF-κB;
Prognosis;
Tumor suppressor
- MeSH:
Adult;
Aged;
Aged, 80 and over;
Basic Helix-Loop-Helix Transcription Factors;
genetics;
Carcinoma, Renal Cell;
genetics;
pathology;
Cell Line, Tumor;
Cell Movement;
genetics;
Disease-Free Survival;
Epithelial-Mesenchymal Transition;
genetics;
Female;
Follistatin-Related Proteins;
genetics;
Gene Expression Regulation, Neoplastic;
genetics;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit;
genetics;
Male;
Middle Aged;
NF-kappa B;
genetics;
Neoplasm Metastasis;
Signal Transduction;
genetics;
Tumor Suppressor Proteins;
genetics
- From:Chinese Journal of Cancer
2018;37(1):2-2
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC.
METHODS:The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients.
RESULTS:FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038).
CONCLUSIONS:FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.
