Work

CAV1 inhibits Xc- system through IFNGR1 to promote ferroptosis to inhibit stemness and improves anti-PD-1 efficacy in breast cancer

Year: 2024

Type: article

Abstract: • This study provided important insights into the mechanism by which CAV1 regulates ferroptosis in breast cancer for the first time. • This study found that CAV1 acts as a scavenger receptor to increase the expression of IFNGR1, thereby enhancing its interaction with IFNγ and inhibiting the occurrence of Xc - system-mediated ferroptosis, providing additional upstream regulatory mechanisms for IFGNR1. • This study demonstrated that CAV1 can serve as a novel target for combinatorial anti-PD-1 therapy, opening up new directions for existing treatment options for breast cancer patients. Breast cancer is the most prevalent malignancy among women worldwide, with breast cancer stem cells (BCSCs) being the primary drivers of metastasis and recurrence. Numerous studies have elucidated the relationship between ferroptosis and cellular stemness, identifying the Xc - system as a key regulatory mechanism governing ferroptosis. However, the interplay between CAV1 and ferroptosis, along with its implications for stemness in breast cancer, remains inadequately understood. This gap in knowledge impedes advancements in targeted therapies for breast cancer. We employed immunohistochemistry and bioinformatics analyses to demonstrate the downregulation of CAV1 in breast cancer tissues. Additionally, we utilized CCK-8 assays, EDU staining, and Transwell assays to assess cell proliferation, migration, and invasion capabilities. Furthermore, we evaluated indicators associated with ferroptosis while examining markers related to stemness through sphere culture experiments and flow cytometry techniques. Our findings indicate that CAV1 expression can induce cell death via ferroptosis while simultaneously inhibiting both cell proliferation and features of stemness by upregulating IFNGR1 and promoting ferroptosis. Moreover, our in vivo experiments revealed that overexpression of CAV1 enhances the efficacy of anti-PD-1 therapy. In conclusion, our study elucidates the regulatory role of CAV1 on ferroptosis within breast cancer contexts; it suppresses BCSC characteristics while positioning CAV1 as a promising therapeutic target for combating this disease.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2024.102149

Authors: Wenhong Liu, Guanghua Luo

Institutions: First Affiliated Hospital of University of South China, University of South China

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,130