title: Oncogenicity of LHX2 in pancreatic ductal adenocarcinoma.
abstract: The LIM proteins (Lhx1, Lhx2, Lhx3 and Lhx4) have been report to play important roles in human development. The function role of Lhxs have been characterized in various tumor tissues as cancer suppressors or promoters in different can status and types. The aim of present study was to clarify the function role of Lhx proteins in human pancreatic ductal adenocarcinoma (PDA). The gene expression profiles of Lhxs was evaluated using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry in human PDA tissues compared with normal pancreatic tissues, which identified the gene overexpression of Lhx2 in PDA. Furthermore, we discovered that Lhx2 promoted cancer cell proliferation in vitro/vivo and elevated β-catenin levels correlated with Lhx2 expression in PDA while the Lhx2 simulated β-catenin activation was required for LMO1's oncogenic effects. Mechanistically, Lhx2 facilitate TCF4 to bind to β-catenin and form a stable Lhx2/TCF4/β-catenin complex and trans-active its downstream target gene. Lhx2 mutations that disrupt the Lhx2-β-catenin interaction partially prevent its function in tumor cells.
authors.affiliation: Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Shanmiao
authors.initials: S
authors.lastname: Gou
authors.forename: Jiongxin
authors.initials: J
authors.lastname: Xiong
authors.forename: Heshui
authors.initials: H
authors.lastname: Wu
authors.forename: Chunyou
authors.initials: C
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015398:Signal Transduction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin