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 PHB21. 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 vivo2.

References
1. Chen, Y.A., et al. (2014), BMC Res Notes, 7:435.
2. Yoshimaru, T., et al. (2013), Nat Commun, 4:2443.