Breast cancer (BC) incidence and associated mortality have increased in tandem with the growth in obesity among the females worldwide. An adipokine, visfatin, has been shown to potentially impact glucose, lipid, and protein metabolism, and promote cancer growth however, the mechanism underlying the effect of visfatin on lipid metabolism dysregulation contributing to BC cell survival, proliferation, and metastasis has not been elucidated. Herein, we have investigated the role of visfatin on the induction of Sterol regulatory element binding protein (SREBP-1) and its upstream and downstream mediators in MCF-7 breast cancer cells. The survival and proliferation was investigated using MTT and Trypan blue assays, cytosolic lipid accumulation was observed using Nile red staining, mRNA and protein expressions were examined using RT-qPCR and western blotting, respectively, and cell cycle analysis was performed using fluorescence-activated cell sorting. Our results indicate that visfatin increased the survival and proliferation of MCF-7 cells in a time- and dose-dependent manner and augmented lipid buildup via activation of SREBP-1 and its associated downstream lipid synthesizing enzymes, at both mRNA and protein levels in MCF-7 cells. Inhibiting SREBP-1 using fatostatin or silencing with siRNA abrogated excessive lipid deposition by suppressing the expression of genes related to lipid synthesis pathway. Further, in-silico study showed high affinity binding of visfatin with epidermal growth factor receptor (EGFR), which was confirmed in an in-vitro study where visfatin increased the phosphorylation of EGFR at tyrosine residue and activated its downstream proteins via phosphorylation of AKT and GSK3β in MCF-7 cells. Inhibition of GSK3β by phosphorylation led to increased activity of SREBP-1 and associated downstream proteins. In summary, SREBP-1 may be a critical player in visfatin-induced lipid synthesis and accumulation in BC cells via activation of EGFR/AKT/GSK3β pathway leading to increased cell survival and proliferation of BC cells.

SLC7A11 controls the uptake of extracellular cystine in exchange for glutamate at a ratio of 1:1, and it is overexpressed in a variety of tumours. Accumulating evidence has shown that the expression of SLC7A11 is fine-tuned at multiple levels, and plays diverse functional and pharmacological roles in tumours, such as cellular redox homeostasis, cell growth and death, and cell metabolism. Many reports have suggested that the inhibition of SLC7A11 expression and activity is favourable for tumour therapy; thus, SLC7A11 is regarded as a potential therapeutic target. However, emerging evidence also suggests that on some occasions, the inhibition of SLC7A11 is beneficial to the survival of cancer cells, and confers the development of drug resistance. In this review, we first briefly introduce the biological properties of SLC7A11, including its structure and physiological functions, and further summarise its regulatory network and potential regulators. Then, focusing on its role in cancer, we describe the relationships of SLC7A11 with tumourigenesis, survival, proliferation, metastasis, and therapeutic resistance in more detail. Finally, since SLC7A11 has been linked to cancer through multiple approaches, we propose that its contribution and regulatory mechanism require further elucidation. Thus, more personalised therapeutic strategies should be adapted when targeting SLC7A11.

This study aimed to evaluate the modulatory role of sex-related hormone estradiol on cancer stem cells with the origin of colorectal adenocarcinoma in vitro. Cancer stem cells were incubated with 100 nM estradiol for 48 h. The cell survival rate was analyzed using the MTT assay. Immunocytochemistry staining of Ki-67 and Inhibin and Apoptosis PCR array were done to measure proliferation/apoptosis. Cell migration was monitored via the Transwell Migration assay. The expression of exosome biogenesis genes was measured using a real-time PCR assay. The fatty acid profile was monitored using gas chromatography. The level of FAK, SQSTM1, ER, and SIRT1 was examined using Western blotting. Cancer stem-endothelial cell interaction was investigated using Surface Plasmon Resonance assay. Data showed no significant differences in cancer stem cell viability and proliferation between control and estradiol-treated groups (p>0.05). PCR array highlighted the up-regulation of both pro- and anti-apoptosis effectors in the treatment group compared to the control cells (p<0.05). Cell migration capacity was increased after treatment with estradiol (p<0.001). Both exocytosis and exosome biogenesis were decreased in cancer stem cells exposed to estradiol (p<0.05). Data showed the reduction of palmitic acid, and increase of Palmitoleic and Linolenic acids in estradiol-treated cells. Estrogen induced estrogen receptor, SQSTM1 proteins and decreased SIRT1 factor after 48 h. Surface Plasmon Resonance revealed the suppression of cancer stem-endothelial cell interaction and affinity. Estradiol could change the migration, juxtacrine and paracrine activities of cancer stem cells, showing the importance of sex-related hormones in the dynamic of cancer development.