Low-Dose Farnesyltransferase Inhibitor Suppresses HIF-1α and Snail Expression in Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro

Tomokazu Tanaka, Yuichi Ikegami, Harumasa Nakazawa, Naohide Kuriyama, Miwa Oki, Jun Ichi Hanai, Vikas P. Sukhatme, Masao Kaneki

研究成果: Article査読

18 被引用数 (Scopus)

抄録

The aggressiveness of triple-negative breast cancer (TNBC), which lacks estrogen receptor, progesterone receptor and epidermal growth factor receptor 2 (HER2), represents a major challenge in breast cancer. Migratory and self-renewal capabilities are integral components of invasion, metastasis and recurrence of TNBC. Elevated hypoxia-inducible factor-1α (HIF-1α) expression is associated with aggressiveness of cancer. Nonetheless, how HIF-1α expression is regulated and how HIF-1α induces aggressive phenotype are not completely understood in TNBC. The cytotoxic effects of farnesyltransferase (FTase) inhibitors (FTIs) have been studied in cancer and leukemia cells. In contrast, the effect of FTIs on HIF-1α expression has not yet been studied. Here, we show that clinically relevant low-dose FTI, tipifarnib (300 nM), decreased HIF-1α expression, migration and tumorsphere formation in human MDA-MB-231 TNBC cells under a normoxic condition. In contrast, the low-dose FTIs did not inhibit cell growth and activity of the Ras pathway in MDA-MB 231 cells. Tipifarnib-induced decrease in HIF-1α expression was associated with amelioration of the Warburg effect, hypermetabolic state, increases in Snail expression and ATP release, and suppressed E-cadherin expression, major contributors to invasion, metastasis and recurrence of TBNC. These data suggest that FTIs may be capable of ameliorating the aggressive phenotype of TNBC by suppressing the HIF-1α-Snail pathway. J. Cell. Physiol. 232: 192–201, 2017.

本文言語English
ページ(範囲)192-201
ページ数10
ジャーナルJournal of Cellular Physiology
232
1
DOI
出版ステータスPublished - 01-01-2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生理学
  • 臨床生化学
  • 細胞生物学

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