Dual Ferroptosis Induction in N2-TANs and TNBC Cells Via FTH1 Targeting: A Therapeutic Strategy for Triple-negative Breast Cancer

Overview

Journal Cell Rep Med

Publisher Cell Press

Date 2025 Jan 14

PMID 39809268

Authors

Yichen Liu

Qingyan Sun

Jingwen Guo

Li Yan

Yue Yan

Yiting Gong

Jiayi Lin

Hu Yuan

Jinmei Jin

Bei Wang

Hongzhuan Chen

Lijun Zhang

Weidong Zhang

Xin Luan

Affiliations

Soon will be listed here.

Abstract

Tumor-associated neutrophils (TANs) play a critical role in the progression and prognosis of triple-negative breast cancer (TNBC), with N2-type TANs known for their pro-tumor characteristics. This study introduces CT-1, a derivative of cryptotanshinone that effectively suppresses TNBC growth while selectively reducing the proportion of N2-type TANs within tumor tissue. Notably, CT-1 induces simultaneous ferroptosis in both N2-type TANs and TNBC cells, a dual mechanism that enhances its therapeutic efficacy. The study identifies ferritin heavy chain 1 (FTH1), a key protein in iron metabolism, as the direct target of CT-1. By targeting FTH1, CT-1 facilitates the interaction between NCOA4 and ferritin, triggering ferritinophagy-mediated ferroptosis. These findings position CT-1 as a promising therapeutic agent, offering a strategy to combat TNBC by inducing ferroptosis in both N2-type TANs and cancer cells. This approach underscores the potential of FTH1 as a therapeutic target for treating TNBC.

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