Glucose Favors Lipid Anabolic Metabolism in the Invasive Breast Cancer Cell Line MDA-MB-231

Abstract

Metabolic reprogramming in tumor cells is considered one of the hallmarks of cancer. Many studies have been carried out in order to elucidate the effects of tumor cell metabolism on invasion and tumor progression. However, little is known about the immediate substrate preference in tumor cells. In this work, we wanted to study this short-time preference using the highly invasive, hormone independent breast cancer cell line MDA-MB-231. By means of Seahorse and uptake experiments, our results point to a preference for glucose. However, although both glucose and glutamine are required for tumor cell proliferation, MDA-MB-231 cells can survive two days in the absence of glucose, but not in the absence of glutamine. On the other hand, the presence of glucose increased palmitate uptake in this cell line, which accumulates in the cytosol instead of going to the plasma membrane. In order to exert this effect, glucose needs to be converted to glycerol-3 phosphate, leading to palmitate metabolism through lipid synthesis, most likely to the synthesis of triacylglycerides. The effect of glucose on the palmitate uptake was also found in other triple-negative, invasive breast cancer cell lines, but not in the non-invasive ones. The results presented in this work suggest an important and specific role of glucose in lipid biosynthesis in triple-negative breast cancer.

Lipid Metabolism and Resistance to Anticancer Treatment

“…Lipogenesis requires the presence of acetyl-CoA, which is mainly derived from the glucose-derived pyruvate into the Krebs cycle ( Figure 1 ). In cancer, the Warburg effect can therefore explain part of the overproduction of fatty acids [ 9 ]. Although glucose supplies carbon units for lipogenesis, alternative carbon sources can be used in case of glycolytic pathway shortage.…”

Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer

“…In contrast to our results in MCF7 cells, we did not observe altered OXPHOS or glycolysis levels in the MDA-MB-231 TAM−R cells. However, MDA-MB-231 cells have been reported to generally rely more on glycolysis for basic cellular metabolism; while MCF7 cells use OXPHOS for 80-90% of their ATP production [22], MDA-MB-231 cells were shown to be less efficient in OXPHOS than MCF7 cells [23], to be highly glycolytic and have a preference for glycolysis [24]. This also supports our finding of higher glycolytic levels in MDA-MB-231 WT compared to MCF7 WT cells.…”

Identification of novel ceRNA networks associated with PD- L1 in head and neck squamous cell carcinoma based on whole-transcriptome sequencing

“…Circulating tumor cells, using CAMs present on their surface to adhere to the endothelium, exited the vasculature with strong blood ow impact force by extravasation, forming metastases at a distance [48]. It has been found that lipid metabolism was reprogrammed in cancer [49] and also played a crucial role in HNSCC [50]. Lipid metabolism supported the survival, proliferation, invasion, and metastasis of cancer cells by promoting membrane formation, energy production, signal transduction, and even mediating drug resistance [51,52].…”