The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation

Elife. 2016 Mar 17:5:e11288. doi: 10.7554/eLife.11288.

Abstract

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.

Keywords: NIFK; casein kinase 1 alpha; cell biology; human; lung cancer; metastasis; runx1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Casein Kinase II / metabolism
  • Cell Proliferation*
  • Disease Models, Animal
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ki-67 Antigen / metabolism
  • Korea
  • Lung Neoplasms / pathology*
  • Mice
  • Neoplasm Metastasis*
  • Nuclear Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • NIFK protein, human
  • Nuclear Proteins
  • beta Catenin
  • CSNK2A1 protein, human
  • Casein Kinase II

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.