Transcription factor YY1 contributes to tumor growth by stabilizing hypoxia factor hif-1α in a P53-independent manner

Shourong Wu, Vivi Kasim, Mitsunobu Kano, Sayaka Tanaka, Shinsuke Ohba, Yutaka Miura, Kanjiro Miyata, Xueying Liu, Matsuhashi Ako Matsuhashi, Ung Il Chung, Li Yang, Kazunori Kataoka, Nobuhiro Nishiyama, Makoto Miyagishi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

In response to hypoxic stress, hypoxia-inducible factor (HIF)-1α is a critical transcription factor regulating fundamental cellular processes, and its elevated expression level and activity are associated with poor outcomes in most malignancies. The transcription factor Yin Yang 1 (YY1) is an important negative regulator of the tumor suppressor factor p53. However, the role of YY1 under tumor hypoxic condition is poorly understood. Herein, we show that inhibition of YY1 reduced the accumulation of HIF-1α and its activity under hypoxic condition, and consequently downregulated the expression of HIF-1α target genes. Interestingly, our results revealed that the downregulation of HIF-1α by inhibiting YY1 is p53-independent. Functionally, the in vivo experiments revealed that inhibition of YY1 significantly suppressed growth of metastatic cancer cells and lung colonization and also attenuated angiogenesis in a p53-null tumor. Collectively, our findings unraveled a novel mechanism by which YY1 inhibition disrupts hypoxia-stimulated HIF-1α stabilization in a p53-independent manner. Therefore, YY1 inhibition could be considered as a potential tumor therapeutic strategy to give consistent clinical outcomes independent of p53 status.

Original languageEnglish
Pages (from-to)1787-1799
Number of pages13
JournalCancer Research
Volume73
Issue number6
DOIs
Publication statusPublished - Mar 15 2013
Externally publishedYes

Fingerprint

Yin-Yang
Hypoxia-Inducible Factor 1
Transcription Factors
Growth
Neoplasms
Down-Regulation
Hypoxia
Lung Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Transcription factor YY1 contributes to tumor growth by stabilizing hypoxia factor hif-1α in a P53-independent manner. / Wu, Shourong; Kasim, Vivi; Kano, Mitsunobu; Tanaka, Sayaka; Ohba, Shinsuke; Miura, Yutaka; Miyata, Kanjiro; Liu, Xueying; Ako Matsuhashi, Matsuhashi; Chung, Ung Il; Yang, Li; Kataoka, Kazunori; Nishiyama, Nobuhiro; Miyagishi, Makoto.

In: Cancer Research, Vol. 73, No. 6, 15.03.2013, p. 1787-1799.

Research output: Contribution to journalArticle

Wu, S, Kasim, V, Kano, M, Tanaka, S, Ohba, S, Miura, Y, Miyata, K, Liu, X, Ako Matsuhashi, M, Chung, UI, Yang, L, Kataoka, K, Nishiyama, N & Miyagishi, M 2013, 'Transcription factor YY1 contributes to tumor growth by stabilizing hypoxia factor hif-1α in a P53-independent manner', Cancer Research, vol. 73, no. 6, pp. 1787-1799. https://doi.org/10.1158/0008-5472.CAN-12-0366
Wu, Shourong ; Kasim, Vivi ; Kano, Mitsunobu ; Tanaka, Sayaka ; Ohba, Shinsuke ; Miura, Yutaka ; Miyata, Kanjiro ; Liu, Xueying ; Ako Matsuhashi, Matsuhashi ; Chung, Ung Il ; Yang, Li ; Kataoka, Kazunori ; Nishiyama, Nobuhiro ; Miyagishi, Makoto. / Transcription factor YY1 contributes to tumor growth by stabilizing hypoxia factor hif-1α in a P53-independent manner. In: Cancer Research. 2013 ; Vol. 73, No. 6. pp. 1787-1799.
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