Abstract
A distinctive feature of cancer cells of various origins involves alterations of the composition of lipids, with significant enrichment in monounsaturated fatty acids. These molecules, in addition to being structural components of newly formed cell membranes of intensely proliferating cancer cells, support tumorigenic signaling. An increase in the expression of stearoyl-CoA desaturase 1 (SCD1), the enzyme that converts saturated fatty acids to ∆9-monounsaturated fatty acids, has been observed in a wide range of cancer cells, and this increase is correlated with cancer aggressiveness and poor outcomes for patients. Studies have demonstrated the involvement of SCD1 in the promotion of cancer cell proliferation, migration, metastasis, and tumor growth. Many studies have reported a role for this lipogenic factor in maintaining the characteristics of cancer stem cells (i.e., the population of cells that contributes to cancer progression and resistance to chemotherapy). Importantly, both the products of SCD1 activity and its direct impact on tumorigenic pathways have been demonstrated. Based on these findings, SCD1 appears to be a significant player in the development of malignant disease and may be a promising target for anticancer therapy. Numerous chemical compounds that exert inhibitory effects on SCD1 have been developed and preclinically tested. The present review summarizes our current knowledge of the ways in which SCD1 contributes to the progression of cancer and discusses opportunities and challenges of using SCD1 inhibitors for the treatment of cancer.
Highlights
One characteristic feature of oncogenic transformation is the deep reprogramming of cellular metabolism
This study showed that high levels of stearoyl-CoA desaturase 1 (SCD1) were associated with an increase in the expression of cancer stem cells (CSCs) markers in cancer tissue that was derived from non-small cell lung cancer (NSCLC) patients who had a more aggressive disease [88]
Application of the SCD1 inhibitor, MF-438, abolished the resistance of melanoma spheroids to these drugs, with simultaneous decreases in the expression of Yes-associated protein (YAP)/TAZ and stem cell markers [87]. Another mechanism implicating SCD1 and the wingless-type MMTV integration site family (Wnt)/β-catenin pathway in CSC-related tumor development has been proposed by Lai et al The authors highlighted that Wnt/β-catenin-driven expression of SCD1, and in turn, monounsaturated fatty acids (MUFAs) synthesis, amplifies Wnt signaling via stabilization of β-catenin and low-density lipoprotein receptor-related proteins 5 and 6 (Lrp5 and 6) mRNA in rodent hepatic stellate cells (HSCs) and tumor-initiating stem cell-like cells (TICs) from the liver [20]
Summary
One characteristic feature of oncogenic transformation is the deep reprogramming of cellular metabolism. This mainly includes limited supplies of nutrients and oxygen that result from a poorly developed vascular system that falls behind intensive tumor growth [5] To overcome these obstacles, cancer cells develop effective lipid metabolism machinery, including an increase in the activity of key lipogenic enzymes, such as adenosine triphosphate (ATP)-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), fatty acid. Higher levels of MUFAs have been found in transformed cells and cancerous tissue [14,15,16,17,18], and have been shown to modulate tumorigenic pathways [19,20,21] Consistent with these findings, SCD1 expression is significantly elevated in various human cancer cells [22,23,24,25]. The present review summarizes our current knowledge of the role of SCD1 in the regulation of cancer cell metabolism and discusses the therapeutic potential of SCD1 inhibitors and challenges to their clinical use for the treatment of human cancer
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