Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

Abstract

Sterol regulatory element binding protein-1 (SREBP-1), a transcription factor with a basic helix–loop–helix leucine zipper, has two isoforms, SREBP-1a and SREBP-1c, derived from the same gene for regulating the genes of lipogenesis, including acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase. Importantly, SREBP-1 participates in metabolic reprogramming of various cancers and has been a biomarker for the prognosis or drug efficacy for the patients with cancer. In this review, we first introduced the structure, activation, and key upstream signaling pathway of SREBP-1. Then, the potential targets and molecular mechanisms of SREBP-1-regulated lipogenesis in various types of cancer, such as colorectal, prostate, breast, and hepatocellular cancer, were summarized. We also discussed potential therapies targeting the SREBP-1-regulated pathway by small molecules, natural products, or the extracts of herbs against tumor progression. This review could provide new insights in understanding advanced findings about SREBP-1-mediated lipogenesis in cancer and its potential as a target for cancer therapeutics.

Fatty acid metabolism: A new therapeutic target for cervical cancer

“…In addition to FASN, another key factor worth noting is sterol regulatory element binding protein 1 (SREBP-1). SREBP-1 activation promotes the expression of FASN, ACC, and SCD1, thereby enhancing lipid synthesis ( 149 ). SREBP binds to SREBP cleavage–activating protein (SCAP) in the ER and is negatively regulated by endogenous sterol levels ( 150 ).…”

“…This releases the N-terminus of SREBP, which eventually binds to sterol response elements (SREs) in the nucleus to activate transcription ( Figure 2 ) ( 150 , 151 ). Several excellent reviews have elucidated the role of SREBP-1 in cancer, and tumor proliferation can be inhibited by knocking down or inhibiting SREBP-1 expression ( 62 , 149 , 152 ). One experiment proved that the level of SREBP-1 was high in CC cells, and quercetin (a naturally occurring polyphenolic flavonoid) could reduce the levels of SREBP-1 and its transcriptional targets by reducing the O-GlcNAcylation of AMPK.…”

Roles of PPARα and PPARγ As Regulator of Free Fatty Acids in Nonalcoholic Steatohepatitis

“…Insulin induces SREBP1c gene expression via AKT signaling and enhances SREBP1c activity. Hepatic SREBP-1c activation leads to the regulation of lipogenic genes such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in the dietrelated condition [24,25]. Elevated glucose levels induce phosphorylation-dependent nuclear relocalization of ChREBP and the ChREBP induces FAS and ACC gene expression [26].…”

The role of noncoding RNAs in cancer lipid metabolism

“…In addition, LINC02570 was upregulated in patients with clinically advanced nasopharyngeal cancer (NPC) and promoted NPC progression by upregulating FASN and sterol regulatory element-binding protein-1 (SREBP-1) through the adsorption of miR-4649-3p ( 56 ). Targeting SREBP-1 Mediated Lipogenesis as Potential Strategies for Cancer ( 57 ).…”