Fatty acids, along with glucose and amino acids, are the main source of energy for cell growth and proliferation. Abnormalities in fatty acid metabolism are commonly seen in cancer.
A growing number of studies have shown that increased ab initio synthesis of fatty acids in tumor cells is a prominent feature in the development of cancer. And the activation of ab initio synthesis is negatively correlated with prognosis and disease-free survival in several tumor types. This phenotype is mainly due to the upregulation of lipogenesis-related genes at multiple levels of transcriptional, translational and post-translational modifications, and enzymatic activity, as well as the impact on oncogene expression due to changes in these genes or lipid metabolism.
The functions of fatty acids in cancer cells include the following:
1. Fatty acid synthesis and cell growth
Actively proliferating tissues require fatty acids for the synthesis of structural lipids. Thus, the induction of lipid synthesis must be closely linked to cell growth, which is a prerequisite for cell division. Inhibition of fatty acid synthesis, for example by inhibiting ACLY with small molecules, impairs the growth of immortalized hematopoietic cells in response to growth factor stimulation.
2. Cardiolipids
Altering fatty acid synthesis and modification can also affect the function of organelles within membrane-containing cells by altering the composition of specific membrane lipids. Cardiolipids are structurally unique phospholipids located primarily in the inner mitochondrial membrane, where they control mitochondrial respiration and act as a signaling platform in the induction of apoptosis.
3、Protein acylation
The abundance and saturation of cellular fatty acids determine the activity of signaling proteins that require acylation function. For example, WNT protein, which is frequently dysregulated in human cancers. Since aberrant activation of the WNT-β-catenin pathway promotes loss of intercellular adhesion and disrupts epithelial cell polarity, regulation of fatty acid desaturation may promote cancer progression and metastasis.
4、Lipid mediators
Lipids can also act as important signaling molecules. For example, the bioactive lipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), which signal through cancer, immune and endothelial cell plasma membrane G protein-coupled LPA receptor (LPAR) autocrine and paracrine mechanisms and stimulate proliferation, migration, inflammation and angiogenesis.
Different types of fatty acids may have different effects on cancer. Saturated fatty acids, trans fatty acids, and Omega-6 PUFA are positively associated with cancer risk or occurrence, while Omega-3 PUFA, a polyunsaturated fatty acid, is believed to have cancer-inhibiting effects. Omega-3 PUFA may exert anti-cancer effects by inhibiting tumor cell proliferation and inducing apoptosis, and by promoting the sensitivity of tumor cells to chemotherapeutic agents.
Creative Proteomics provides fatty acid analysis services. Our lipidomics analysis platform can detect cancer biomarkers, analyze the role and specific mechanisms of genes related to lipid metabolism in cancer, and investigate the signaling pathways that may be involved. We aim to help identify more key lipids and lipid molecules in different types of cancer, and explore the relationship between abnormal expression of related metabolic genes and enzymes and the development of various cancers, thus providing new ideas for cancer prevention, diagnosis, treatment and mechanism research.
