AhR signaling suppresses tumor progression and metastatic potential of breast cancer cells by inducing ubiquitin ligase CHIP.

• Project/Area Number: 25893022
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: University of Tsukuba
• Principal Investigator: HIYOSHI Hiromi 筑波大学, 生命環境系, 助教 (10406530)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 乳がん / AhR / ダイオキシン受容体

Outline of Final Research Achievements

Breast cancer has poor survival and high recurrence rates for aggressive metastatic disease. There is no preferred agent for metastasis of breast cancer. In this study, I show that aryl hydrocarbon receptor (AhR) ligand, YL-109 has ability to inhibit breast cancer cell growth and invasiveness in vitro and in vivo. YL-109 increased the expression of carboxyl terminus of Hsp70-interacting protein (CHIP), which suppresses tumorigenic and metastatic potential of breast cancer cells. YL-109 induced CHIP transcription because of the recruitment of the AhR to upstream of CHIP gene in breast cancer cells. Consistently, the antitumor effects of YL-109 were depressed by CHIP or AhR knockdown in breast cancer cells. Taken together, my findings indicate that a novel agent YL-109 inhibits cell growth and metastatic potential by inducing CHIP expression through AhR signaling in breast cancer cells. It suggests that YL-109 is a potential candidate for breast cancer therapy.

Research Products

• [Journal Article] CHIP acts as a capacitor of phenotypic heterogeneity in breast cancer cells (2014)
  • Author(s): Tsuchiya M, Nakajima Y, Waku T, Hiyoshi H, Morishita T, Furumai R, Hayashi Y, Kishimoto H, Kimura K, Yanagisawa J.
  • Journal Title: Oncogene Volume: なし Issue: 35 Pages: 1-8
  • DOI: 10.1038/onc.2014.387
  • Peer Reviewed
• [Journal Article] 2-(4-Hydroxy-3-methoxyphenyl)-benzothiazole suppresses tumor progression and metastatic potential of breast cancer cells by inducing ubiquitin ligase CHIP (2014)
  • Author(s): Hiromi Hiyoshi, Natsuka Goto, Mai Tsuchiya, Keisuke Iida, Yuka Nakajima, Naoya Hirata, Yasunari Kanda, Kazuo Nagasawa and Junn Yanagisawa
  • Journal Title: Sci. Rep. Volume: 4 Issue: 1 Pages: 7095-7095
  • DOI: 10.1038/srep07095
  • NAID: 120007136531
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic rRNA Transcription Regulates High-Fat-Diet-Induced Obesity. (2014)
  • Author(s): Oie S, Matsuzaki K, Yokoyama W, Tokunaga S, Waku T, Han SI, Iwasaki N, Mikogai A, Yasu zawa-Tanaka K, Kishimoto H, H iyoshi H, Nakajima Y, Araki T, Kimura K, Yanagisawa J, Murayama A.
  • Journal Title: Cell Report Volume: 7(3) Issue: 3 Pages: 807-820
  • DOI: 10.1016/j.celrep.2014.03.038
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transfoming Growth Factor-beta Signaling via Estrogen Receptor α (2014)
  • Author(s): Natsuka Goto, Hiromi Hiyoshi, Ichiaki Ito, Keisuke Iida, Yuka Nakajima, Kazuo Nagasawa and Junn Yanagisawa
  • Journal Title: Journal of Cancer Volume: 5 Issue: 5 Pages: 336-343
  • DOI: 10.7150/jca.7202
  • Peer Reviewed / Open Access
• [Journal Article] Reply: Comment on 'Quiescence and yH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase': ouabain and cancer. (2013)
  • Author(s): Hiyoshi H, Johnsen JI, Andang M, Uhlen P.
  • Journal Title: Br. J. Cancer Volume: 108 Issue: 10 Pages: 2191-2191
  • DOI: 10.1038/bjc.2013.235
  • Open Access