title: LINE-1 ORF-1p functions as a novel HGF/ETS-1 signaling pathway co-activator and promotes the growth of MDA-MB-231 cell.
abstract: Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro-oncogene LINE-1. It is involved in the development and progression of several human carcinomas, such as hepatocellular carcinoma and lung and breast cancers. The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in regulation of cancer cell proliferation, metastasis and invasion. The biological function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling pathway in regulation of human breast cancer proliferation remains largely unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional activity and increased expression of downstream genes of ETS-1. Interaction between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays. LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1 ORF-1p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated that LINE-1 ORF-1p may be a novel ETS-1 coactivator and molecular target for therapy of human triple negative breast cancer.
authors.affiliation: College of Clinical Medicine, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Chunping
authors.initials: C
authors.lastname: Wang
authors.forename: Yinying
authors.initials: Y
authors.lastname: Lu
authors.forename: Xudong
authors.initials: X
authors.lastname: Gao
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003850:Deoxyribonuclease I / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D011401:Promoter Regions, Genetic; D060066:Protein Interaction Maps; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D017228:Hepatocyte Growth Factor; D003850:Deoxyribonuclease I; C538849:LINE-1 endonuclease, human; D020781:Matrix Metalloproteinase 1
keywords: HGF/ETS-1 signaling; LINE-1 ORF-1p; Protein–protein interaction; Transcriptional activity; Triple negative breast cancer