From molecular mechanisms of breast cancer cell growth to novel therapeutic strategies

  • Toyomasa Katagiri’s group in Tokushima University discovered BIG3, a novel regulator of estrogen signaling, and demonstrated that its interaction with PHB2, a known repressor of estrogen receptor (ER), played a critical role in cell growth of ER-positive breast cancer cells. BIG3 is a huge protein, however, and it was difficult to work with biochemically. By a combination of protein structure and interaction-site predictions, we were able to present a model of how BIG3 would interact with PHB2 [2014-2]. Based on this prediction, an inhibitory peptide was designed and shown to suppress the growth of ER-positive breast cancer cells and also to make them susceptible to tamoxifen, an anti-estrogen drug, both in vitro and in vivo [2013-1].



  1. 2014年9月22日 乳癌細胞増殖の分子機構解明から創薬へ 読売新聞 朝刊
  2. Chen, Y.-A., Murakami, Y., Ahmad, S., Yoshimaru, T., Katagiri, T., & Mizuguchi, K. 2014 Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) is predicted to interact with its partner through an ARM-type α-helical structure. BMC Research Notes 7, 435 doi


  1. Yoshimaru, T., Komatsu, M., Matsuo, T., Chen, Y.-A., Murakami, Y., Mizuguchi, K., Mizohata, E., Inoue, T., Akiyama, M., Yamaguchi, R., Imoto, S., Miyano, S., Miyoshi, Y., Sasa, M., Nakamura, Y., & Katagiri, T. 2013 Targeting BIG3–PHB2 interaction to overcome tamoxifen resistance in breast cancer cells. Nature Communications 4 doi