Lipid metabolism in tumor microenvironment: novel therapeutic targets

Abstract

Bioactive lipid molecules have been proposed to play important roles linking obesity/metabolic syndrome and cancers. Studies reveal that aberrant lipid metabolic signaling can reprogram cancer cells and non-cancer cells in the tumor microenvironment, contributing to cancer initiation, progression, metastasis, recurrence, and poor therapeutic response. Existing evidence indicates that controlling lipid metabolism can be a potential strategy for cancer prevention and therapy. By reviewing the current literature on the lipid metabolism in various cancers, we summarized major lipid molecules including fatty acids and cholesterol as well as lipid droplets and discussed their critical roles in cancer cells and non-cancer in terms of either promoting- or anti-tumorigenesis. This review provides an overview of the lipid molecules in cellular entities and their tumor microenvironment, adding to the existing knowledge with lipid metabolic reprogramming in immune cells and cancer associated cells. Comprehensive understanding of the regulatory role of lipid metabolism in cellular entities and their tumor microenvironment will provide a new direction for further studies, in a shift away from conventional cancer research. Exploring the lipid-related signaling targets that drive or block cancer development may lead to development of novel anti-cancer strategies distinct from traditional approaches for cancer prevention and treatment.

Mechanism of Cytotoxic Action of Gold Nanorods Photothermal Therapy for A549 Cell

“…Cancer cells use lipid metabolism to obtain energy, biofilm components, and signaling molecules needed for proliferation, survival, invasion, metastasis, tumor response, and cancer treatment. Numerous studies showed that lipid metabolism disorders play a key role in the progression of NPs exposure toxicity. ,− In this experimental group, 18-hydroxyoleate and 9,10-epoxystearic acid were up-regulated and phosphocholine was downregulated, while the levels of the remaining metabolites did not change significantly. Both metabolites in the GNR group were significantly up-regulated, implying that these may help in clearing cancer cells.…”

Altered tumor signature and T‐cell profile after chemotherapy reveal new therapeutic opportunities in high‐grade serous ovarian carcinoma

“…Lipid metabolism in tumor cells and stroma has been linked to tumor progression and drug resistance. 46,47 It is also noteworthy that endothelial expression of FABP4, PRCP, and KLF4, which are upregulated after chemotherapy, has been linked to vascular injury repair. 48,49 Thus these genes may represent potential targets for anti-angiogenic therapies.…”

“…Second, genes and subpopulations associated with lipid uptake and metabolism were upregulated in the post‐treatment fibroblasts and endothelial cells. Lipid metabolism in tumor cells and stroma has been linked to tumor progression and drug resistance 46,47 . It is also noteworthy that endothelial expression of FABP4 , PRCP , and KLF4 , which are upregulated after chemotherapy, has been linked to vascular injury repair 48,49 .…”

Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response

“…PUFAs, especially LC-PUFAs such as arachidonic acid (AA), eicosatetraenoic acid (EPA), and docosahexaenoic acid (DHA), are important signaling molecules and key components of biomembrane phospholipids (22,23). PUFAs and their derivatives have been implicated to play broad functions in cancer impacting various stages from tumorigenesis to progression and metastasis (24)(25)(26)(27)(28). Previous research has shown that Fatty Acid Desaturase 1 (FADS1), a rate-limiting enzyme in LC-PUFA bioproduction, plays a significant role in the growth of various cancer cells (13) and is overexpressed in colon, pancreas, breast, and laryngeal cancers (29).…”