Tumor suppressor HLJ1 binds and functionally alters nucleophosmin via activating enhancer binding protein 2α complex formation
Journal
Cancer Research
Journal Volume
70
Journal Issue
4
Pages
1656-1667
Date Issued
2010
Author(s)
Abstract
HLJ1, a member of the heat shock protein 40 chaperone family, is a newly identified tumor suppressor that has been implicated in tumorigenesis and metastasis in non-small cell lung cancer. However, the mechanism of HLJ1 action is presently obscure. In this study, we report that HLJ1 specifically interacts with the nuclear protein nucleophosmin (NPM1), forming a multiprotein complex that alters the nucleolar distribution and oligomerization state of NPM1. Enforced accumulation of NPM1 oligomers by overexpression in weakly invasive but high HLJ1-expressing cells induced the activity of signal transducer and activator of transcription 3 (STAT3) and increased cellular migration, invasiveness, and colony formation. Furthermore, silencing HLJ1 accelerated NPM1 oligomerization, inhibited the activity of transcription corepressor activating enhancer binding protein 2α (AP-2α), and increased the activities of matrix metalloproteinase-2 (MMP-2) and STAT3. Our findings suggest that HLJ1 switches the role of NPM1, which can act as tumor suppressor or oncogene, by modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and recruiting AP-2α to the MMP-2 promoter. ?2010 AACR.
SDGs
Other Subjects
activating enhancer binding protein 2alpha; binding protein; gelatinase A; heterodimer; nucleophosmin; STAT3 protein; tumor suppressor HLJ1; tumor suppressor protein; unclassified drug; article; cancer cell culture; cancer inhibition; cell invasion; cell migration; chromatin immunoprecipitation; colony formation; complex formation; enhancer region; gene silencing; human; human cell; lung adenocarcinoma; oligomerization; oncogene; priority journal; protein analysis; protein binding; protein function; protein interaction; real time polymerase chain reaction; Western blotting; Adenocarcinoma; Cell Nucleus; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; HSP40 Heat-Shock Proteins; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Multiprotein Complexes; Neoplasm Invasiveness; Nuclear Proteins; Protein Binding; Protein Multimerization; Protein Structure, Tertiary; Protein Transport; Transcription Factor AP-2; Transfection; Tumor Cells, Cultured; Tumor Suppressor Proteins
Type
journal article