In many tissues, stearoyl-CoA desaturase 1 (SCD1) catalyzes the biosynthesis of monounsaturated fatty acids (MUFAS), (i.e., palmitoleate and oleate) from their saturated fatty acid (SFA) precursors (i.e., palmitate and stearate), influencing cellular membrane physiology and signaling, leading to broad effects on human physiology. In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment for various diseases, such as nonalcoholic steatohepatitis, Alzheimer’s disease, cancer, and skin disorders. Sterculic acid (SA) is a cyclopropene fatty acid originally found in the seeds of the plant Sterculia foetida with numerous biological activities. On the one hand, its ability to inhibit stearoyl-CoA desaturase (SCD) allows its use as a coadjuvant of several pathologies where this enzyme has been associated. On the other hand, additional effects independently of its SCD inhibitory properties, involve anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD). This review aims to summarize the mechanisms by which SA exerts its actions and to highlight the emerging areas where this natural compound may be of help for the development of new therapies for human diseases.

Invadopodia are actin-rich protrusions developed by transformed cells in 2D/3D environments that are implicated in extracellular matrix (ECM) remodeling and degradation. These structures have an undoubted association with cancer invasion and metastasis because invadopodium formation in vivo is a key step for intra/extravasation of tumor cells. Invadopodia are closely related to other actin-rich structures known as podosomes, which are typical structures of normal cells necessary for different physiological processes during development and organogenesis. Invadopodia and podosomes are included in the general term ‘invadosomes,’ as they both appear as actin puncta on plasma membranes next to extracellular matrix metalloproteinases, although organization, regulation, and function are slightly different. Integrins are transmembrane proteins implicated in cell–cell and cell–matrix interactions and other important processes such as molecular signaling, mechano-transduction, and cell functions, e.g., adhesion, migration, or invasion. It is noteworthy that integrin expression is altered in many tumors, and other pathologies such as cardiovascular or immune dysfunctions. Over the last few years, growing evidence has suggested a role of integrins in the formation of invadopodia. However, their implication in invadopodia formation and adhesion to the ECM is still not well known. This review focuses on the role of integrins in invadopodium formation and provides a general overview of the involvement of these proteins in the mechanisms of metastasis, taking into account classic research through to the latest and most advanced work in the field.

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In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood. In order to provide insights into those mechanisms, genome-wide transcriptomic analyses were carried out in mRPE cells exposed to SA for 24 h. Integrative functional enrichment analysis of genome-wide expression data provided biological insight about the protective mechanisms induced by SA. On the one hand, pivotal genes related to fatty acid biosynthesis, steroid biosynthesis, cell death, actin-cytoskeleton reorganization and extracellular matrix-receptor interaction were significantly downregulated by exposition to SA. On the other hand, genes related to fatty acid degradation and beta-oxidation were significantly upregulated. In conclusion, SA administration to RPE cells regulates crucial pathways related to cell proliferation, inflammation and cell death that may be of interest for the treatment of ocular diseases.

Age-related macular degeneration (AMD) is an incurable disease associated with aging that destroys sharp and central vision. Increasing evidence implicates both systemic and local inflammation in the pathogenesis of AMD. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is currently the first-line therapy for choroidal neovascularization in AMD patients. However, a high number of patients do not show satisfactory responses to anti-VEGF treatment after three injections. Predictive treatment response models are one of the most powerful tools for personalized medicine. Therefore, the application of these models is very helpful to predict the optimal treatment for an early application on each patient. We analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) from AMD patients before treatment to identify biomarkers of response to ranibizumab. A classification model comprised of four mRNAs and one miRNA isolated from PBMCs was able to predict the response to ranibizumab with high accuracy (Area Under the Curve of the Receiver Operating Characteristic curve = 0.968), before treatment. We consider that our classification model, based on mRNA and miRNA from PBMCs allows a robust prediction of patients with insufficient response to anti-VEGF treatment. In addition, it could be used in combination with other methods, such as specific baseline characteristics, to identify patients with poor response to anti-VEGF treatment to establish patient-specific treatment plans at the first visit.

Age-related macular degeneration is the main cause of irreversible vision in developed countries, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the current gold standard treatment today. Although anti-VEGF treatment results in important improvements in the course of this disease, there is a considerable number of patients not responding to the standardized protocols. The knowledge of how a patient will respond or how frequently retreatment might be required would be vital in planning treatment schedules, saving both resource utilization and financial costs, but today, there is not an ideal biomarker to use as a predictive response to ranibizumab therapy. Whole blood and blood mononuclear cells are the samples most studied; however, few reports are available on other important biofluid samples for studying this disease, such as aqueous humor. Moreover, the great majority of studies carried out to date were focused on the search for SNPs in genes related to AMD risk factors, but miRNAs, proteomic and metabolomics studies have rarely been conducted in anti-VEGF-treated samples. Here, we propose that genomic, proteomic and/or metabolomic markers could be used not alone but in combination with other methods, such as specific clinic characteristics, to identify patients with a poor response to anti-VEGF treatment to establish patient-specific treatment plans.

Sterculic acid (SA) is a cyclopropenoid fatty acid isolated from Sterculia foetida seeds. This molecule is a well-known inhibitor of SCD1 enzyme, also known as ∆9-desaturase, which main function is related to lipid metabolism. However, recent studies have demonstrated that it also modifies many other pathways and the underlying gene expression. SCD overexpression, or up-regulated activity, has been associated with tumor aggressiveness and poor prognosis in many cancer types. Scd1 down-regulation, with different inhibitors or molecular strategies, reduces tumor cell survival and cell proliferation, as well as the chemoresistance associated with cancer stem cell presence. However, SA effects over cancer cell migration and extracellular matrix or adhesion molecules have not been described in cancer cells up to now. We used different migration assays and qPCR gene expression analysis to evaluate the effects of SA treatment in cancer cells. The results reveal that SA induces tumoral cell death at high doses, but we also observed that lower SA-treatments induce cell adhesion-migration capacity reduction as a result of modifications in the expression of genes related to integrins and extracellular matrix compounds. Overall, the functional and transcriptomic findings suggest that SA could represent a new inhibitor activity of epithelial to mesenchymal transition.

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