Breast Cancer: Targets and Therapy (Jun 2017)
High glucose levels promote the proliferation of breast cancer cells through GTPases
Abstract
Yilin Hou,1 Man Zhou,1 Jing Xie,1 Ping Chao,1 Qiyu Feng,2 Jun Wu1 1Department of Endocrinology, The Third Hospital of Wuhan (Tongren Hospital of Wuhan University), Wuhan, People’s Republic of China; 2Eastern Hepatobiliary Surgery Institute, National Center for Liver Cancer, Shanghai, People’s Republic of China Abstract: Hyperglycemia or diabetes mellitus (DM), which is characterized by high blood glucose levels, has been linked to an increased risk of cancer for years. However, the underlying molecular mechanisms of the pathophysiological link are not yet fully understood. In this study, we demonstrate that high glucose levels promote the proliferation of breast cancer cells by stimulating epidermal growth factor receptor (EGFR) activation and the Rho family GTPase Rac1 and Cdc42 mediate the corresponding signaling induced by high glucose levels. We further show that Cdc42 promotes EGFR phosphorylation by blocking EGFR degradation, which may be mediated by the Cbl proteins, whereas the Rac1-mediated EGFR phosphorylation is independent of EGFR degradation. Our findings elucidate a part of the underlying molecular mechanism of the link between high glucose levels and tumorigenesis in breast cancer and may provide new insights on the therapeutic strategy for cancer patients with diabetes or hyperglycemia. Keyword: hyperglycemia, breast cancer, GTPases, Rac1, Cdc42, EGFR
