An Overview of Heavy Chain Ferritin in Cancer

³ Department of Obstetrics and Gynecology, Hubei Clinical Medicine Research Center for Individualized Cancer Diagnosis and Therapy, The First Affiliated Hospital of Yangtze University, 434023 Jingzhou, Hubei, China

⁴ Department of Obstetrics and Gynecology, Hubei Clinical Medicine Research Center for Individualized Cancer Diagnosis and Therapy, The First Affiliated Hospital of Yangtze University, 434023 Jingzhou, Hubei, China

⁵ Department of Physiology, The First Affiliated Hospital of Yangtze University, 434023 Jingzhou, Hubei, China

^*Correspondence: cunjiany@163.com (Cunjian Yi); ivansblue@sina.com (Fuyuan Yang)
^†These authors contributed equally.

Front. Biosci. (Landmark Ed) 2023, 28(8), 182; https://doi.org/10.31083/j.fbl2808182

Submitted: 18 January 2023 | Revised: 2 March 2023 | Accepted: 10 March 2023 | Published: 28 August 2023

This is an open access article under the CC BY 4.0 license.

Abstract

As a spherical protein that acts as a repository for intracellular iron, Ferritin is the most important iron storage form and is known to influence tumor immunity. Unbound ferritin is composed of 24 subunits, made up of ferritin light chain (FTL) and ferritin heavy chain (FTH). Ferritin can be automatically put together to form hollow nanocages that measure 12 nm around the outside and 8 nm around the inside. Cancer causes the second-most deaths worldwide, effective elimination of tumor cells while protecting normal cells is the foundation of modern tumor therapy. To this end, the innate tumor-targeting activity of human FTH1, first identified ten years ago, is highly appealing. Unmodified human FTH1 binds to its receptor, transferrin receptor 1 (TfR1), which is frequently overexpressed in cancer cells. FTH1-TfR1 binding permits improved drug efficacy by promoting ferritin-mediated targeted delivery. In addition, FTH is also associated with the prognosis of multiple typies of cancer. The level of FTH1 is significantly and positively correlated with the infiltration of tumor-associated macrophages. FTH1 also plays an important role in regulating the tumor immunity of solid cancer. As such, FTH1 has been extensively applied in the targeted delivery of anticancer drugs, diagnostic molecules (e.g., radioisotopes and fluorophones), and inorganic nanoparticles (NPs) to tumors.This article reviews the role of FTH in cancer and its potential as a therapeutic target.

Keywords

cancer

ferritin

FTH

tumor

Funding

2022CA48/major project of Jingzhou Science and Technology Plan

CIMF-F-H001-313/Exchange Fund of China International Medical Association

WJ2019M085/Hubei Province health and family planning scientific research project

Fund of Hubei Clinical Medicine Research Center for individualized cancer diagnosis and therapy

Figures

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Fig. 1.

Intracellular iron homeostasis. Ferritin acts as an iron oxidase and iron is internalized and sequestered in the ferritin mineral core, converting Fe ${}^{2+}$ to Fe ${}^{3+}$ . Reactive substances (yellow balls) can directly damage DNA and proteins. Iron absorption in the duodenum is controlled via the expression and transport activity of divalent metal transporter 1 (DMT1) on the luminal side of enterocytes and by ferroportin, the sole known iron exporter on the basal side, which transfers iron into the bloodstream. Abbreviations: Hp, hepcidin; Tf, Transferrin.

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