Inhibition of PP2A in MCF-7 cells leads to hormone-independent growth

Endocrine therapy is the most effective systemic treatment for patients with HR+ breast cancer. Oestrogen deprivation therapy with nonsteroidal third-generation AIs is more effective than tamoxifen for postmenopausal women with HR+ advanced breast cancer. Unfortunately, the efficacy of the treatment is often limited by the onset of resistance, which is almost inevitable in patients with advanced disease. Occasionally, AIs treatment resistant ERα positive breast cancers are observed in the course of endocrine therapy. The findings of the previous study revealed crosstalk between the IGF-I signalling pathway and ERα in breast cancer cells. Abnormally activation of ERα is dependent on phosphorylation of the serine residues S104, S106, S118, and S167 located in the amino terminal A/B domain of ERα4. Small-molecule inhibition and targeted knockdown of S6 kinase 1 (S6K1) blocked IGF-1 induced phosphorylation of ERα at residue S167. Inhibition of S6K1 kinase activity consequently ablated IGF-1 stimulated S6K1/ERα association and subsequent ERα target gene transcript ion. 〈Original article〉