title: The role of stearoyl-coenzyme A desaturase 1 in clear cell renal cell carcinoma.
abstract: This study aimed to investigate the correlations of stearoyl-coenzyme A desaturase 1 (SCD-1) with clear cell renal cell carcinoma (ccRCC) severity and PI3K-AKT-mTOR signaling pathway. From 2004 to 2006, tumor tissue and normal pericarcinomatous tissue from ccRCC samples were collected from ccRCC patients at Renji Hospital of Shanghai Jiaotong University. The expression of SCD-1 in the collected ccRCC samples and four cell lines (A498, 769-P, 786-O, and CAKI) was detected by Western blot. The correlation between SCD-1 expression and ccRCC severity was also analyzed by immunohistochemistry. Stable 786-O and 769-P ccRCC cells expressing SCD-1 short hairpin RNA (shRNA) were constructed, and the expression of proteins in the PI3K-AKT-mTOR signaling pathway was also detected. Finally, the inhibitory effect of PI3K-AKT-mTOR inhibitors (PI103, MK2206, rapamycin, AZD8055, and RAD001) on ccRCC cells stably expressing SCD-1 shRNA was also measured. Higher SCD-1 expression level was observed in ccRCC tissues compared with normal tissues. SCD-1 expression level was the highest in 786-O. SCD-1 expression was positively correlated with the tumor-node-metastasis (TNM) stage, grade of tumor cells, and lymphatic metastasis. There were no changes in the expression of AKT, ERK, PI3K, and PDK1. Significant differences were observed in the expression of p-AKT (at the Ser473 and Thr308 site), p-ERK, and two mTOR downstream molecules (4E-BP1 and p-P70S6K1) in cells stably expressing SCD-1 shRNA. PI103 and AZD8055 could enhance the inhibitory effect of SCD-1 interference on proliferation and migration of 786-O and 769-P cells. AZD8055 is recommended for the combined ccRCC treatment with shRNA interference.
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai, 200127, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai, 200127, China.
authors.forename: Yujian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai, 200127, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai, 200127, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Song
authors.affiliation: Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai, 200127, China. med-zhangjin@vip.sina.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai, 200127, China. hyrrenji2@aliyun.com.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000068338:Everolimus / Q000737:chemistry; D005260:Female; D005663:Furans / Q000737:chemistry; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D009025:Morpholines / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D034622:RNA Interference; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*
chemical_list: D005663:Furans; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D009025:Morpholines; C522973:PI103; D011725:Pyridines; D011743:Pyrimidines; C546624:(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol; D000068338:Everolimus; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase
keywords: AZD8055; Clear cell renal cell carcinoma; MK2206; PI103; PI3K-AKT-mTOR signaling pathway; RAD001; Rapamycin; Stearoyl-coenzyme A desaturase 1