Abstract
Reprogramming of cellular energy metabolism is widely accepted to be a cancer hallmark. The deviant energetic metabolism of cancer cells-known as the Warburg effect-consists in much higher rates of glucose uptake and glycolytic oxidation coupled with the production of lactic acid, even in the presence of oxygen. Consequently, cancer cells have higher glucose needs and thus display a higher sensitivity to glucose deprivation-induced death than normal cells. So, inhibitors of glucose uptake are potential therapeutic targets in cancer. Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women worldwide. Overexpression of facilitative glucose transporters (GLUT), mainly GLUT1, in breast cancer cells is firmly established, and the consequences of GLUT inhibition and/or knockout are under investigation. Herein we review the compounds, both of natural and synthetic origin, found to interfere with uptake of glucose by breast cancer cells, and the consequences of interference with that mechanism on breast cancer cell biology. We will also present data where the interaction with GLUT is exploited in order to increase the efficiency or selectivity of anticancer agents, in breast cancer cells.
Highlights
IntroductionAccording to the last Global Cancer Statistics (GLOBOCAN 2018), breast cancer represented 12%
According to the last Global Cancer Statistics (GLOBOCAN 2018), breast cancer represented 12%of all cancers, being the second most frequent cancer worldwide, after lung cancer, and caused about7% of the total cancer deaths in 2018 [1]
A similar negative effect of GLUT1 short hairpin RNA (shRNA) on glucose uptake was found in two other triple-negative breast cancer cell lines (MDA-MB-231 and Hs578T), together with a decrease in cell proliferation, migration, and invasion, which was concluded to result from GLUT1-mediated modulation of Epidermal Growth Factor Receptor (EGFR)/Mitogen-Activated Protein Kinase (MAPK), and integrin β1/Sarcoma Virus (Src)/FAK signaling pathways [67]
Summary
According to the last Global Cancer Statistics (GLOBOCAN 2018), breast cancer represented 12%. Of all cancers, being the second most frequent cancer worldwide, after lung cancer, and caused about. Breast cancer is the leading type of cancer and the leading cause of cancer death worldwide [1]. Screening programs and adjuvant chemotherapy have had a significant impact on the prognosis of breast cancer patients, having significantly improved their overall survival, disease-free survival, and death rates related to breast-cancer since the early 1990s [2,3]. Efforts must continue in order to reduce the incidence and the mortality and treatment-associated morbidities associated with this disease. In this context, discovery of new molecular targets and the refinement of lead compounds constitute a priority in breast cancer research
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