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

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Aug 1

PMID 35912181

Authors

Qiushi Zhao

Xingyu Lin

Guan Wang

Affiliations

Soon will be listed here.

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.

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References

Wen S, Niu Y, Lee S, Yeh S, Shang Z, Gao H . Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells. Mol Carcinog. 2016; 55(12):2278-2290. DOI: 10.1002/mc.22468. View

Talebi A, Dehairs J, Rambow F, Rogiers A, Nittner D, Derua R . Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy. Nat Commun. 2018; 9(1):2500. PMC: 6021375. DOI: 10.1038/s41467-018-04664-0. View

Fhu C, Ali A . Fatty Acid Synthase: An Emerging Target in Cancer. Molecules. 2020; 25(17). PMC: 7504791. DOI: 10.3390/molecules25173935. View

Porstmann T, Griffiths B, Chung Y, Delpuech O, Griffiths J, Downward J . PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene. 2005; 24(43):6465-81. DOI: 10.1038/sj.onc.1208802. View

Brovkovych V, Izhar Y, Danes J, Dubrovskyi O, Sakallioglu I, Morrow L . Fatostatin induces pro- and anti-apoptotic lipid accumulation in breast cancer. Oncogenesis. 2018; 7(8):66. PMC: 6107643. DOI: 10.1038/s41389-018-0076-0. View

Gholkar A, Cheung K, Williams K, Lo Y, Hamideh S, Nnebe C . Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division. J Biol Chem. 2016; 291(33):17001-8. PMC: 5016105. DOI: 10.1074/jbc.C116.737346. View

Rome S, Lecomte V, Meugnier E, Rieusset J, Debard C, Euthine V . Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle. Physiol Genomics. 2008; 34(3):327-37. DOI: 10.1152/physiolgenomics.90211.2008. View

Zhou C, Qian W, Ma J, Cheng L, Jiang Z, Yan B . Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1. Cell Prolif. 2018; 52(1):e12514. PMC: 6430460. DOI: 10.1111/cpr.12514. View

Santana-Codina N, Marce-Grau A, Muixi L, Nieva C, Marro M, Sebastian D . GRP94 Is Involved in the Lipid Phenotype of Brain Metastatic Cells. Int J Mol Sci. 2019; 20(16). PMC: 6720951. DOI: 10.3390/ijms20163883. View

10.

Li X, Chen Y, Hu P, Huang W . Fatostatin displays high antitumor activity in prostate cancer by blocking SREBP-regulated metabolic pathways and androgen receptor signaling. Mol Cancer Ther. 2014; 13(4):855-66. PMC: 4084917. DOI: 10.1158/1535-7163.MCT-13-0797. View

11.

Yang Y, Morin P, Han W, Chen T, Bornman D, Gabrielson E . Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. Exp Cell Res. 2003; 282(2):132-7. DOI: 10.1016/s0014-4827(02)00023-x. View

12.

Wang C, Ma J, Zhang N, Yang Q, Jin Y, Wang Y . The acetyl-CoA carboxylase enzyme: a target for cancer therapy?. Expert Rev Anticancer Ther. 2015; 15(6):667-76. DOI: 10.1586/14737140.2015.1038246. View

13.

Icard P, Wu Z, Fournel L, Coquerel A, Lincet H, Alifano M . ATP citrate lyase: A central metabolic enzyme in cancer. Cancer Lett. 2019; 471:125-134. DOI: 10.1016/j.canlet.2019.12.010. View

14.

Varghese J, Patel R, Yadav U . Sterol regulatory element binding protein (SREBP) -1 mediates oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation through NLRP3 inflammasome activation. Cell Signal. 2018; 53:316-326. DOI: 10.1016/j.cellsig.2018.10.020. View

15.

Suh J, Gong E, Kim J, Lee I, Choi H, Lee K . Sterol regulatory element-binding protein-1c represses the transactivation of androgen receptor and androgen-dependent growth of prostatic cells. Mol Cancer Res. 2008; 6(2):314-24. DOI: 10.1158/1541-7786.MCR-07-0354. View

16.

Wu S, Naar A . SREBP1-dependent de novo fatty acid synthesis gene expression is elevated in malignant melanoma and represents a cellular survival trait. Sci Rep. 2019; 9(1):10369. PMC: 6637239. DOI: 10.1038/s41598-019-46594-x. View

17.

Wang G, Li Z, Li X, Zhang C, Peng L . RASAL1 induces to downregulate the SCD1, leading to suppression of cell proliferation in colon cancer via LXRα/SREBP1c pathway. Biol Res. 2019; 52(1):60. PMC: 6918686. DOI: 10.1186/s40659-019-0268-x. View

18.

Shafiee M, Mongan N, Seedhouse C, Chapman C, Deen S, Abu J . Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer. Acta Obstet Gynecol Scand. 2017; 96(5):556-562. DOI: 10.1111/aogs.13106. View

19.

Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F . SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004; 86(11):839-48. DOI: 10.1016/j.biochi.2004.09.018. View

20.

Yu X, Lin Q, Wu Z, Zhang Y, Wang T, Zhao S . ZHX2 inhibits SREBP1c-mediated de novo lipogenesis in hepatocellular carcinoma via miR-24-3p. J Pathol. 2020; 252(4):358-370. DOI: 10.1002/path.5530. View