Search

Y-box binding protein 1 (YB-1) is a regulatory protein associated with oncogenesis and poor prognosis in patients with cancer. In the cell, YB-1 functions as a DNA and RNA binding protein that promotes or suppresses expression of target genes. The cancer-promoting activity of YB-1 is mediated through its activation of oncogenes and repression of tumor suppressor genes. Lipogenic enzyme stearoyl-CoA desaturase (SCD1) drives the production of endogenous monounsaturated fatty acids (MUFAs) in cells and protects against toxic buildup of saturated fatty acids. Clear cell renal cell carcinoma (ccRCC) is often characterized by aberrantly high SCD1 expression and cytosolic accumulation of unsaturated fatty acids. In the present study, a proteomics screen of cells treated with inhibitors of SCD1 supported a potential relationship between YB-1 and SCD1. It was revealed that the presence of MUFAs led to increased protein synthesis and increased expression of high molecular weight forms of YB-1 in ccRCC cells, but not in non-tumorigenic cells. Ectopic expression of YB-1 led to decreased expression levels of SCD1 protein and mRNA in ccRCC cell lines. Conversely, targeted knockdown of YB-1 increased SCD1 mRNA abundance. Analysis of ccRCC patient data from The Cancer Proteome Atlas database showed YB-1 expression was negatively associated with survival, whereas SCD1 was associated with improved survival. These data suggested an antagonistic relationship between YB-1 and SCD1 that may influence survival of patients with ccRCC.

According to the National Institutes of Health, clear cell renal cell carcinoma (ccRCC) is the most common type of Renal Cell Carcinoma (RCC), making up approximately 75% of total renal carcinoma cases. Clear cell Renal Cell Carcinoma is characterized by a significant accumulation of lipids in the cytoplasm, which allows light from microscopes to pass through giving them a “clear” phenotype. Many of these lipids are in the form of fatty acids, both free and incorporated into lipid droplets. RCC is typically associated with a poor prognosis due to the lack of specific symptoms. Some symptoms include blood in urine, fever, lump on the side, weight loss, fatigue, to name a few; all of which can be associated with non-specific, non-cancerous, health conditions that contribute to difficult diagnosis. Treatment of RCC has typically been centered around radical nephrectomy as the standard of care, but due to the potentially small size of lesions and the possibility of causing surgically induced chronic kidney disease, treatments have shifted to more cautious, less invasive approaches. These approaches include active surveillance, nephron-sparing surgery, and other minimally invasive techniques like cryotherapy and renal ablation. Although these techniques have had the desired effect of reducing the number of surgeries, there is still considerable potential for renal impairment and the chance that tumors can grow out of control without surgery. With the difficulty that surrounds the treatment of ccRCC and its considerably high mortality rate amongst urological cancers, it is important to look for novel approaches to improve patient outcomes. This review looks at available literature and our data that suggests the lipogenic enzyme stearoyl-CoA desaturase may be more beneficial to patient survival than once thought. As our understanding of the importance of lipids in cell metabolism and longevity matures, it is important to present new perspectives that present a new understanding of ccRCC and the role of lipids in survival mechanisms engaged by transformed cells during cancer progression. In this review, we provide evidence that pharmacological inhibition of lipid desaturation in renal cancer patients is not without risk, and that the presence of unsaturated fatty acids may be a beneficial factor in patient outcomes. Although more direct experimental evidence is needed to make definitive conclusions, it is clear that the work reviewed herein should challenge our current understanding of cancer biology and may inform novel approaches to the diagnosis and treatment of ccRCC.