title: Oncogenicity of LHX4 in colorectal cancer through Wnt/β-catenin/TCF4 cascade.
abstract: The LHX genes play an important role in a number of developmental processes. Potential roles of LHXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the function role of LHXs in the human colorectal cancer (CRC). The gene expression changes of LHXs in CRC tissues compared with noncancerous colorectal tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. And we identified the gene LHX4 that were significantly upregulated in CRC by QRT-PCR analysis and immunohistochemistry. Furthermore, we discovered that LHX4 promoted cancer cell proliferation in vitro, and LHX4 expression correlated with elevated β-catenin levels in CRC and β-catenin function was required for LHX4's oncogenic effects. Mechanistically, LHX4 facilitate TCF4 to bind to β-catenin and form a stable LHX4/TCF4/β-catenin complex and transactive its downstream target gene. LHX4 mutations that disrupt the LHX4-β-catenin interaction partially prevent its function in tumor cells. All in all, LHX4 is a commonly activated tumor promoter that activate Wnt/β-catenin signaling in cancer cells of CRC.
authors.affiliation: Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Hangfangdian, Haidian District, Beijing, 100038, People's Republic of China.
authors.forename: Nier
authors.initials: N
authors.lastname: Cha
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.forename: Shengzhi
authors.initials: S
authors.lastname: Xie
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Gao
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin