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

研究成果: 雜誌貢獻文章

13 引文 (Scopus)

摘要

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.
原文英語
文章編號e11288
期刊eLife
5
發行號MARCH2016
DOIs
出版狀態已發佈 - 三月 17 2016

指紋

Casein Kinases
Catenins
Cell proliferation
Nuclear Proteins
Cell Proliferation
Neoplasm Metastasis
Lung Neoplasms
Neoplasms
Transcription Factors
Cell Movement
Down-Regulation
Proteins

ASJC Scopus subject areas

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

引用此文

Lin, T. C., Su, C. Y., Wu, P. Y., Lai, T. C., Pan, W. A., Jan, Y. H., ... 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

The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation. / Lin, Tsung Chieh; Su, Chia Yi; Wu, Pei Yu; Lai, Tsung Ching; Pan, Wen An; Jan, Yi Hua; Chang, Yu Chang; Yeh, Chi-Tai; Chen, Chi-Long; Ger, Luo Ping; Chang, Hong Tai; Yang, Chih Jen; Huang, Ming Shyan; Liu, Yu Peng; Lin, Yuan-Feng; Shyy, John Y J; Tsai, M. D.; Hsiao, Michael.

於: eLife, 卷 5, 編號 MARCH2016, e11288, 17.03.2016.

研究成果: 雜誌貢獻文章

Lin, TC, Su, CY, Wu, PY, Lai, TC, Pan, WA, Jan, YH, Chang, YC, Yeh, C-T, Chen, C-L, Ger, LP, Chang, HT, Yang, CJ, Huang, MS, Liu, YP, Lin, Y-F, Shyy, JYJ, Tsai, MD & Hsiao, M 2016, 'The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation', eLife, 卷 5, 編號 MARCH2016, e11288. https://doi.org/10.7554/eLife.11288
Lin, Tsung Chieh ; Su, Chia Yi ; Wu, Pei Yu ; Lai, Tsung Ching ; Pan, Wen An ; Jan, Yi Hua ; Chang, Yu Chang ; Yeh, Chi-Tai ; Chen, Chi-Long ; Ger, Luo Ping ; Chang, Hong Tai ; Yang, Chih Jen ; Huang, Ming Shyan ; Liu, Yu Peng ; Lin, Yuan-Feng ; Shyy, John Y J ; Tsai, M. D. ; Hsiao, Michael. / The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation. 於: eLife. 2016 ; 卷 5, 編號 MARCH2016.
@article{6f7e2cc9fad946bea113a74a74c42a51,
title = "The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation",
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.",
author = "Lin, {Tsung Chieh} and Su, {Chia Yi} and Wu, {Pei Yu} and Lai, {Tsung Ching} and Pan, {Wen An} and Jan, {Yi Hua} and Chang, {Yu Chang} and Chi-Tai Yeh and Chi-Long Chen and Ger, {Luo Ping} and Chang, {Hong Tai} and Yang, {Chih Jen} and Huang, {Ming Shyan} and Liu, {Yu Peng} and Yuan-Feng Lin and Shyy, {John Y J} and Tsai, {M. D.} and Michael Hsiao",
year = "2016",
month = "3",
day = "17",
doi = "10.7554/eLife.11288",
language = "English",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "MARCH2016",

}

TY - JOUR

T1 - The nucleolar protein NIFK promotes cancer progression via ck1α/β-catenin in metastasis and ki-67-dependent cell proliferation

AU - Lin, Tsung Chieh

AU - Su, Chia Yi

AU - Wu, Pei Yu

AU - Lai, Tsung Ching

AU - Pan, Wen An

AU - Jan, Yi Hua

AU - Chang, Yu Chang

AU - Yeh, Chi-Tai

AU - Chen, Chi-Long

AU - Ger, Luo Ping

AU - Chang, Hong Tai

AU - Yang, Chih Jen

AU - Huang, Ming Shyan

AU - Liu, Yu Peng

AU - Lin, Yuan-Feng

AU - Shyy, John Y J

AU - Tsai, M. D.

AU - Hsiao, Michael

PY - 2016/3/17

Y1 - 2016/3/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84961904098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961904098&partnerID=8YFLogxK

U2 - 10.7554/eLife.11288

DO - 10.7554/eLife.11288

M3 - Article

C2 - 26984280

AN - SCOPUS:84961904098

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

IS - MARCH2016

M1 - e11288

ER -