Navigating Heme Pathways: the Breach of Heme Oxygenase and Hemin in Breast Cancer

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2024 Sep 17

PMID 39287890

Authors

Valeria Consoli

Valeria Sorrenti

Maria Gulisano

Mariarita Spampinato

Luca Vanella

Affiliations

Soon will be listed here.

Abstract

Breast cancer remains a significant global health challenge, with diverse subtypes and complex molecular mechanisms underlying its development and progression. This review comprehensively examines recent advances in breast cancer research, with a focus on classification, molecular pathways, and the role of heme oxygenases (HO), heme metabolism implications, and therapeutic innovations. The classification of breast cancer subtypes based on molecular profiling has significantly improved diagnosis and treatment strategies, allowing for tailored approaches to patient care. Molecular studies have elucidated key signaling pathways and biomarkers implicated in breast cancer pathogenesis, shedding light on potential targets for therapeutic intervention. Notably, emerging evidence suggests a critical role for heme oxygenases, particularly HO-1, in breast cancer progression and therapeutic resistance, highlighting the importance of understanding heme metabolism in cancer biology. Furthermore, this review highlights recent advances in breast cancer therapy, including targeted therapies, immunotherapy, and novel drug delivery systems. Understanding the complex interplay between breast cancer subtypes, molecular pathways, and innovative therapeutic approaches is essential for improving patient outcomes and developing more effective treatment strategies in the fight against breast cancer.

References

Song X, Wang X, Liu Z, Yu Z . Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib. Front Oncol. 2021; 10:597434. PMC: 7785974. DOI: 10.3389/fonc.2020.597434. View

Nagappan A, Kim J, Jung D, Jung M . Cryptotanshinone from the Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways. Int J Mol Sci. 2020; 21(1). PMC: 6981483. DOI: 10.3390/ijms21010265. View

Salemme V, Centonze G, Cavallo F, Defilippi P, Conti L . The Crosstalk Between Tumor Cells and the Immune Microenvironment in Breast Cancer: Implications for Immunotherapy. Front Oncol. 2021; 11:610303. PMC: 7991834. DOI: 10.3389/fonc.2021.610303. View

Al Khamees M, Alqurain A, Alsaleh A, Alhashem Y, Alsaffar N, Alibrahim N . Prevalence of Iron Deficiency and its Association With Breast Cancer in Premenopausal Compared to Postmenopausal Women in Al Ahsa, Saudi Arabia. Cancer Inform. 2023; 22:11769351231172589. PMC: 10201173. DOI: 10.1177/11769351231172589. View

cermak J, Balla J, JACOB H, Balla G, Enright H, Nath K . Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy. Cancer Res. 1993; 53(21):5308-13. View

Wang L, Zhang S, Wang X . The Metabolic Mechanisms of Breast Cancer Metastasis. Front Oncol. 2021; 10:602416. PMC: 7817624. DOI: 10.3389/fonc.2020.602416. View

Dey S, Sayers C, Verginadis I, Lehman S, Cheng Y, Cerniglia G . ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. J Clin Invest. 2015; 125(7):2592-608. PMC: 4563676. DOI: 10.1172/JCI78031. View

Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P . Breast cancer. Nat Rev Dis Primers. 2019; 5(1):66. DOI: 10.1038/s41572-019-0111-2. View

Giraldo N, Sanchez-Salas R, Peske J, Vano Y, Becht E, Petitprez F . The clinical role of the TME in solid cancer. Br J Cancer. 2018; 120(1):45-53. PMC: 6325164. DOI: 10.1038/s41416-018-0327-z. View

Roberson R, Kussick S, Vallieres E, Chen S, Wu D . Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res. 2005; 65(7):2795-803. DOI: 10.1158/0008-5472.CAN-04-1270. View

10.

Higgins M, Stearns V . Understanding resistance to tamoxifen in hormone receptor-positive breast cancer. Clin Chem. 2009; 55(8):1453-5. DOI: 10.1373/clinchem.2009.125377. View

11.

Jiang W, Chen L, Guo X, Cheng C, Luo Y, Wang J . Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy. Theranostics. 2022; 12(6):2987-3006. PMC: 8965496. DOI: 10.7150/thno.71693. View

12.

Sikora E, Czarnecka-Herok J, Bojko A, Sunderland P . Therapy-induced polyploidization and senescence: Coincidence or interconnection?. Semin Cancer Biol. 2020; 81:83-95. DOI: 10.1016/j.semcancer.2020.11.015. View

13.

Colo G, Schweitzer K, Oresti G, Alonso E, Chavez L, Mascaro M . Proteomic analysis of the effect of hemin in breast cancer. Sci Rep. 2023; 13(1):10091. PMC: 10284804. DOI: 10.1038/s41598-023-35125-4. View

14.

Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P . How basal are triple-negative breast cancers?. Int J Cancer. 2008; 123(1):236-40. DOI: 10.1002/ijc.23518. View

15.

Hung Y, Ouyang C, Ping X, Qi Y, Wang Y, Kung H . Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. J Biomed Sci. 2023; 30(1):32. PMC: 10201738. DOI: 10.1186/s12929-023-00924-4. View

16.

Doi K, Akaike T, Fujii S, Tanaka S, Ikebe N, Beppu T . Induction of haem oxygenase-1 nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth. Br J Cancer. 1999; 80(12):1945-54. PMC: 2363152. DOI: 10.1038/sj.bjc.6690624. View

17.

Zhu X, Huang S, Zeng L, Ma J, Sun S, Zeng F . HMOX-1 inhibits TGF-β-induced epithelial-mesenchymal transition in the MCF-7 breast cancer cell line. Int J Mol Med. 2017; 40(2):411-417. PMC: 5505025. DOI: 10.3892/ijmm.2017.3027. View

18.

Glei M, Klenow S, Sauer J, Wegewitz U, Richter K, Pool-Zobel B . Hemoglobin and hemin induce DNA damage in human colon tumor cells HT29 clone 19A and in primary human colonocytes. Mutat Res. 2005; 594(1-2):162-71. DOI: 10.1016/j.mrfmmm.2005.08.006. View

19.

Ishikawa S, Tamaki S, Ohata M, Arihara K, Itoh M . Heme induces DNA damage and hyperproliferation of colonic epithelial cells via hydrogen peroxide produced by heme oxygenase: a possible mechanism of heme-induced colon cancer. Mol Nutr Food Res. 2010; 54(8):1182-91. DOI: 10.1002/mnfr.200900348. View