title: CYP2S1 depletion enhances colorectal cell proliferation is associated with PGE2-mediated activation of β-catenin signaling.
abstract: Colorectal epithelial cancer is one of the most common cancers in the world and its 5-year survival rate is still relatively low. Cytochrome P450 (CYP) enzymes in epithelial cells lining the alimentary tract play an important role in the oxidative metabolism of a wide range of xenobiotics, including (pro-)carcinogens and endogenous compounds. Although CYP2S1, a member of CYP family, strongly expressed in many extrahepatic tissues, the role of CYP2S1 in cancer remains unclear. To investigate whether CYP2S1 involves in colorectal carcinogenesis, cell proliferation was analyzed in HCT116 cells depleted of CYP2S1 using small hairpin interfering RNA. Our data show that CYP2S1 knockdown promotes cell proliferation through increasing the level of endogenous prostaglandin E2(PGE2). PGE2, in turn, reduces phosphorylation of β-catenin and activates β-catenin signaling, which contributes to the cell proliferation. Furthermore, CYP2S1 knockdown increase tumor growth in xenograft mouse model. In brief, these results demonstrate that CYP2S1 regulates colorectal cancer growth through associated with PGE2-mediated activation of β-catenin signaling.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; College of Life Science, Anhui Normal University, Wuhu 241000, Anhui, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: College of Life Science, Anhui Normal University, Wuhu 241000, Anhui, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Minle
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tong
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xuhan
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Life Sciences & Biotechnology, Shanghai JiaoTong University, Shanghai 200240, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yan
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: helinhelin@gmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: clwan@sjtu.edu.cn.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D003106:Colon / Q000166:cytology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051176:beta Catenin; D003577:Cytochrome P-450 Enzyme System; C422564:CYP2S1 protein, human; D015232:Dinoprostone
keywords: CYP2S1; Colorectal cancer cell; HCT116; PGE2; ShRNA; β-catenin