Background: A dysregulation of cholesterol homeostasis is often seen in various cancer cell types, and elevated cholesterol content and that of its metabolites appears to be crucial for cancer progression and metastasis. Cholesterol is a precursor of various steroid hormones and a key plasma membrane component especially in lipid-rafts, also modulating many intracellular signaling pathways.Methods: To provide an insight of dysregulated cholesterol regulatory genes, their transcript levels were analyzed in different cancers and their influence was correlated with the overall survival of cancer patients using cancer database analysis.Results: This analysis found a set of genes (e.g., ACAT1, RXRA, SOAT1 and SQLE) that were not only often dysregulated, but also had been associated with poorer overall survival in most cancer types. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed elevated SQLE and SOAT1 transcript levels and downregulated expression of RXRA and ACAT1 genes in triple negative breast cancer tissues compared to adjacent control tissues, indicating that this dysregulated expression of the gene signature is a diagnostic marker for breast cancer.
Conclusion:For the first time, the present study identified a gene signature associated with the dysregulation of cholesterol homeostasis in cancer cells that may not only be used as a diagnostic marker, but also comprise a promising drug target for the advancement of cancer therapy.
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Despite advances in treatment, individuals diagnosed with cancer are often at risk of suffering from metastasis, tumor recurrence, therapy resistance, and off-target toxicities from conventional chemo-, radio-, and endocrine- therapies. Drugs with potent anticancer and antimetastatic activity, but with milder side effects, can be combined with conventional therapies to increase efficacy, reduced therapy resistance, and decrease toxicity. Substantial data from epidemiological, cell culture, animal and clinical studies have established anticancer potential of nontoxic omega-3 fatty acids. This paper highlights the beneficial effects of omega-3 fatty acid treatment when used in combination with conventional therapies protect against metastasis, enhance therapeutic efficacy, and prevent the off-target toxicity caused by conventional therapies. These omega-3 fatty acids target therapy-induced central players NF-κB, and ROS to prevent drug-associated metastasis, therapy resistance, and off-target toxicities.
In spite of recent advances made in understanding its progression, cancer is still a leading cause of death across the nations. Molecular pathophysiology of these cancer cells largely differs depending on cancer types and even within the same tumor. Pathological mineralization/calcification is seen in various tissues including breast, prostate, and lung cancer. Osteoblast‐like cells derived after trans‐differentiation of mesenchymal cells usually drive calcium deposition in various tissues. This study aims to explore the presence of osteoblast‐like potential in lung cancer cells and its prevention. ALP assay, ALP staining, nodule formation, RT‐PCR, RT‐qPCR, and western blot analysis experiments were carried out in lung cancer A549 cells to achieve said objective. Expressions of various osteoblast markers (e.g., ALP, OPN, RUNX2, and Osterix) along with osteoinducer genes (BMP‐2 and BMP‐4) were observed in A549 cells. Moreover, ALP activity and ability leading to nodule formation revealed the presence of osteoblast‐like potential in lung cancer cells. Here, BMP‐2 treatment increased expressions of osteoblast transcription factors such as RUNX2 and Osterix, enhanced ALP activity, and augmented calcification in this cell line. It was also observed that antidiabetic metformin inhibited BMP‐2 mediated increase in osteoblast‐like potential and calcification in these cancer cells. The current study noted that metformin blocked BMP‐2 mediated increase in epithelial to mesenchymal transition (EMT) in A549 cells. The above findings for the first time unravel that A549 cells possess osteoblast‐like potential which drives lung cancer calcification. Metformin might prevent BMP‐2 induced osteoblast‐like phenotype of the lung cancer cells with concomitant inhibition of EMT to inhibit lung cancer tissue calcification.
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