eLife, 2016-03, Vol.5
2016
Details
- Autor(en) / Beteiligte
- Titel
- The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation
- Ist Teil von
- eLife, 2016-03, Vol.5
- Ort / Verlag
- England: eLife Sciences Publications Ltd
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2050-084XeISSN: 2050-084XDOI: 10.7554/eLife.11288Titel-ID: cdi_doaj_primary_oai_doaj_org_article_0d4368b0109b4676a724a8c829493a57
- Format
- –
- Schlagworte
- Animals, beta Catenin - metabolism, Casein, casein kinase 1 alpha, Casein Kinase II - metabolism, Cell Biology, Cell cycle, Cell growth, Cell migration, Cell Proliferation, Clinical medicine, Cyclin-dependent kinases, Disease Models, Animal, Gene expression, Genomics, Hospitals, Humans, Intracellular Signaling Peptides and Proteins - metabolism, Ki-67 Antigen - metabolism, Kinases, Korea, Lung cancer, Lung Neoplasms - pathology, Medical prognosis, Medical research, Medicine, Metastases, Metastasis, Mice, Neoplasm Metastasis, NIFK, Nuclear Proteins - metabolism, Nucleoli, Phosphorylation, Proteins, runx1, Runx1 protein, β-Catenin