The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation

Tsung Chieh Lin, Chia Yi Su, Pei Yu Wu, Tsung Ching Lai, Wen An Pan, Yi Hua Jan, Yu Chang Chang, Chi-Tai Yeh, Chi-Long Chen, Luo Ping Ger, Hong Tai Chang, Chih Jen Yang, Ming Shyan Huang, Yu Peng Liu, Yuan-Feng Lin, John Y J Shyy, M. D. Tsai, Michael Hsiao

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 1a (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1a 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.

Original languageEnglish
Article numbere11288
JournaleLife
Volume5
Issue numberMARCH2016
DOIs
Publication statusPublished - Mar 17 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

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    Lin, T. C., Su, C. Y., Wu, P. Y., Lai, T. C., Pan, W. A., Jan, Y. H., Chang, Y. C., Yeh, C-T., Chen, C-L., Ger, L. P., Chang, H. T., Yang, C. J., Huang, M. S., Liu, Y. P., Lin, Y-F., Shyy, J. Y. J., Tsai, M. D., & Hsiao, M. (2016). The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation. eLife, 5(MARCH2016), [e11288]. https://doi.org/10.7554/eLife.11288