HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk
Autor: | Hengyu Li, Pinghua Yang, JingHan Wang, Jin Zhang, Qianyun Ma, Yingjie Jiang, Yani Wu, Tao Han, Daimin Xiang |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Cancer Research
Tumor-associated macrophages TGF-β1/SMAD3/HLF/IL-6/JAK2/STAT3 pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens Antineoplastic Agents Triple Negative Breast Neoplasms Hematology Basic-Leucine Zipper Transcription Factors Oncology Triple-negative breast cancer Drug Resistance Neoplasm GGT1 Tumor Microenvironment Humans Ferroptosis Female Diseases of the blood and blood-forming organs RC633-647.5 Molecular Biology Letter to the Editor RC254-282 |
Zdroj: | Journal of Hematology & Oncology, Vol 15, Iss 1, Pp 1-6 (2022) Journal of Hematology & Oncology |
ISSN: | 1756-8722 |
Popis: | Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment (TME) which are closely associated with the tumor malignant progression. However, the regulatory mechanisms by which TAMs influence the progression of triple-negative breast cancer (TNBC) remain unclear. Here, we report that hepatic leukemia factor (HLF) acts as a novel oncoprotein in TNBC. We found that HLF was regulated by transforming growth factor-beta1 (TGF-β1) that is secreted by TAMs. Then, HLF transactivated gamma-glutamyltransferase 1 (GGT1) to promote the ferroptosis resistance, thus driving TNBC cell proliferation, metastasis and cisplatin resistance. Reciprocally, IL-6 produced by TNBC cells activated the JAK2/STAT3 axis to induce TGF-β1 secretion by TAMs, thus constituted a feed-forward circuit. The accuracy of TNBC patient prognosis could be improved by employing a combination of HLF and GGT1 values. Thus, our findings document that the interactive dialogue between TNBC cells and TAMs promotes sustained activation of HLF in tumor cells through the IL-6-TGF-β1 axis. Subsequently, HLF promotes the ferroptosis resistance in TNBC cells via GGT1 and ultimately facilitates the malignant tumor progression. Our study provides a potential target for the treatment of TNBC. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-021-01223-x. |
Databáze: | OpenAIRE |
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