The Impact of Lipid Metabolism on Breast Cancer: a Review About Its Role in Tumorigenesis and Immune Escape

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2023 Jun 27

PMID 37370164

Authors

Diandra Zipinotti Dos Santos

Josiany Carlos de Souza

Tatiana Massariol Pimenta

Barbara da Silva Martins

Roberto Silva Ribeiro Junior

Solenny Maria Silva Butzene

Nayara Gusmao Tessarolo

Paulo Morais Lyra Cilas Jr

Ian Victor Silva

Leticia B A Rangel

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer (BC) is the second most frequent type of cancer in the world and most common among women, configuring a major challenge to global health. BC is a complex and heterogeneous disease that can be subdivided into distinct tumor types based on the expression of molecular markers predicting patient outcomes and response to therapy. A growing number of studies have tried to expand the known markers by investigating the association of altered lipid metabolism with BC immune escape, progression, and metastasis. In this review, we describe the metabolic peculiarities of each BC subtype, understanding how this influences its aggressiveness and identifying whether these intrinsic vulnerabilities of each subtype can play a role in therapeutic management and may affect immune system cells in the tumor microenvironment.

Conclusion: The evidence suggests so far that when changes occur in lipid pathways, it can affect the availability of structural lipids for membrane synthesis, lipid synthesis, and degradation that contribute to energy homeostasis and cell signaling functions. These findings will guide the next steps on the path to understanding the mechanisms underlying how lipids alterations are related to disparities in chemotherapeutic response and immune escape in BC. Video Abstract.

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References

Milgraum L, Witters L, Pasternack G, Kuhajda F . Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res. 1998; 3(11):2115-20. View

Luo X, Cheng C, Tan Z, Li N, Tang M, Yang L . Emerging roles of lipid metabolism in cancer metastasis. Mol Cancer. 2017; 16(1):76. PMC: 5387196. DOI: 10.1186/s12943-017-0646-3. View

Dignam J, Wieand K, Johnson K, Fisher B, Xu L, Mamounas E . Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst. 2003; 95(19):1467-76. PMC: 4676737. DOI: 10.1093/jnci/djg060. View

Xia L, Oyang L, Lin J, Tan S, Han Y, Wu N . The cancer metabolic reprogramming and immune response. Mol Cancer. 2021; 20(1):28. PMC: 7863491. DOI: 10.1186/s12943-021-01316-8. View

Camarda R, Zhou A, Kohnz R, Balakrishnan S, Mahieu C, Anderton B . Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat Med. 2016; 22(4):427-32. PMC: 4892846. DOI: 10.1038/nm.4055. View

Hultsch S, Kankainen M, Paavolainen L, Kovanen R, Ikonen E, Kangaspeska S . Association of tamoxifen resistance and lipid reprogramming in breast cancer. BMC Cancer. 2018; 18(1):850. PMC: 6109356. DOI: 10.1186/s12885-018-4757-z. View

Yu W, Lei Q, Yang L, Qin G, Liu S, Wang D . Contradictory roles of lipid metabolism in immune response within the tumor microenvironment. J Hematol Oncol. 2021; 14(1):187. PMC: 8572421. DOI: 10.1186/s13045-021-01200-4. View

Ye L, Zhang B, Seviour E, Tao K, Liu X, Ling Y . Monoacylglycerol lipase (MAGL) knockdown inhibits tumor cells growth in colorectal cancer. Cancer Lett. 2011; 307(1):6-17. DOI: 10.1016/j.canlet.2011.03.007. View

Eiriksson F, Nohr M, Costa M, Bodvarsdottir S, Ogmundsdottir H, Thorsteinsdottir M . Lipidomic study of cell lines reveals differences between breast cancer subtypes. PLoS One. 2020; 15(4):e0231289. PMC: 7156077. DOI: 10.1371/journal.pone.0231289. View

10.

Yao P, Ni Y, Liu C . Long Non-Coding RNA 691 Regulated PTEN/PI3K/AKT Signaling Pathway in Osteosarcoma Through miRNA-9-5p. Onco Targets Ther. 2020; 13:4597-4606. PMC: 7250307. DOI: 10.2147/OTT.S249827. View

11.

Li C, Yang L, Zhang D, Jiang W . Systematic review and meta-analysis suggest that dietary cholesterol intake increases risk of breast cancer. Nutr Res. 2016; 36(7):627-35. DOI: 10.1016/j.nutres.2016.04.009. View

12.

Zheng Y, Ren S, Zhang Y, Liu S, Meng L, Liu F . Circular RNA circWWC3 augments breast cancer progression through promoting M2 macrophage polarization and tumor immune escape via regulating the expression and secretion of IL-4. Cancer Cell Int. 2022; 22(1):264. PMC: 9396792. DOI: 10.1186/s12935-022-02686-9. View

13.

Boutilier A, Elsawa S . Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci. 2021; 22(13). PMC: 8268869. DOI: 10.3390/ijms22136995. View

14.

Yang T, Zhao J, Liu F, Li Y . Lipid metabolism and endometrial receptivity. Hum Reprod Update. 2022; 28(6):858-889. DOI: 10.1093/humupd/dmac026. View

15.

Agresti R, Meneghini E, Baili P, Minicozzi P, Turco A, Cavallo I . Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study. Breast Cancer Res Treat. 2016; 157(1):179-89. DOI: 10.1007/s10549-016-3802-3. View

16.

Hatzivassiliou G, Zhao F, Bauer D, Andreadis C, Shaw A, Dhanak D . ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005; 8(4):311-21. DOI: 10.1016/j.ccr.2005.09.008. View

17.

Lastwika K, Wilson 3rd W, Li Q, Norris J, Xu H, Ghazarian S . Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer. Cancer Res. 2015; 76(2):227-38. DOI: 10.1158/0008-5472.CAN-14-3362. View

18.

Wu Q, Ishikawa T, Sirianni R, Tang H, McDonald J, Yuhanna I . 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep. 2013; 5(3):637-45. PMC: 3950897. DOI: 10.1016/j.celrep.2013.10.006. View

19.

Antalis C, Arnold T, Rasool T, Lee B, Buhman K, Siddiqui R . High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation. Breast Cancer Res Treat. 2009; 122(3):661-70. DOI: 10.1007/s10549-009-0594-8. View

20.

Barnard M, Boeke C, Tamimi R . Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta. 2015; 1856(1):73-85. DOI: 10.1016/j.bbcan.2015.06.002. View