title: Orphan nuclear receptor Nur77 promotes colorectal cancer invasion and metastasis by regulating MMP-9 and E-cadherin.
abstract: Nur77, an orphan member of the nuclear receptor superfamily, has been implicated in tumorigenesis. However, its contributions to colorectal cancer (CRC) invasion and metastasis are largely under characterized. Here, we present the first evidence that the invasion and metastasis of CRC is regulated by Nur77. High expression of Nur77 was observed in clinical CRC tissues, and this elevated expression was significantly associated with advanced tumor, lymph nodes, distant metastasis stage (P = 0.003), lymph node metastasis (P = 0.001) and poor survival (P = 0.03). Overexpression of Nur77 in CRC cells enhanced cell invasion in vitro, whereas knockdown of Nur77 diminished cell invasion and metastasis both in vitro and in vivo. In studying the possible mechanism by which overexpression of Nur77 contributes to CRC invasion and metastasis, we observed that the nuclear protein Nur77 promoted the expression of matrix metalloproteinase (MMP)-9, a novel downstream target of Nur77, and subsequently decreased the expression of E-cadherin. Examination of clinical samples further showed that Nur77 expression is positively correlated with MMP-9, whereas negatively correlated with E-cadherin. Interestingly, Nur77-mediated CRC invasion via MMP-9 and E-cadherin could be mimicked by some metastasis-inducible factors including hypoxia and prostaglandin E2. Collectively, our study demonstrated that Nur77 could promote the invasion and metastasis of CRC cells through regulation of MMP-9/E-cadherin signaling. These observations provide a possible new strategy for potentially treating or preventing the metastasis of CRC through targeting of Nur77.
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China.
authors: Jing-Ru
authors: JR
authors: Wang
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China, Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China and.
authors: Wen-Juan
authors: WJ
authors: Gan
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China.
authors: Xiu-Ming
authors: XM
authors: Li
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China.
authors: Yuan-Yuan
authors: YY
authors: Zhao
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors: Ying
authors: Y
authors: Li
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China.
authors: Xing-Xing
authors: XX
authors: Lu
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China, wuhua@suda.edu.cn jianmingli@suda.edu.cn.
authors: Jian-Ming
authors: JM
authors: Li
authors: Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China, wuhua@suda.edu.cn.
authors: Hua
authors: H
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015820:Cadherins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020780:Matrix Metalloproteinase 9