Myeloid PTEN loss affects the therapeutic response by promoting stress granule assembly and impairing phagocytosis by macrophages in breast cancer

Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN lo...

Full description

Saved in:
Bibliographic Details
Published in:Cell death discovery 2024-07, Vol.10 (1), p.344-14, Article 344
Main Authors: Li, Yan, Xu, Chao, Qian, Xiaojun, Wang, Gang, Han, Chaoqiang, Hua, Hui, Dong, Menghao, Chen, Jian, Yu, Haiyang, Zhang, Rutong, Feng, Xiaoxi, Yang, Zhenye, Pan, Yueyin
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
631/67/327
631/80/304
AKT protein
Antitumor activity
Apoptosis
Biochemistry
Biomedical and Life Sciences
Bone marrow
Breast cancer
Cell activation
Cell Biology
Cell Cycle Analysis
Chromosome 10
Drug resistance
EGR-1 protein
Immunity
Life Sciences
Macrophages
Oxidative stress
Phagocytes
Phagocytosis
PTEN protein
Stem Cells
TOR protein
Tumor suppressor genes
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN loss has been reported to impair antitumour immunity. In this study, we revealed a novel mechanism by which myeloid PTEN potentially affects antitumour immunity in BRCA. We detected accelerated stress granule (SG) assembly under oxidative stress in PTEN-deficient bone marrow-derived macrophages (BMDMs) through the EGR1-promoted upregulation of TIAL1 transcription. PI3K/AKT/mTOR (PAM) pathway activation also promoted SG formation. ATP consumption during SG assembly in BMDMs impaired the phagocytic ability of 4T1 cells, potentially contributing to the disruption of antitumour immunity. In a BRCA neoadjuvant cohort, we observed a poorer response in myeloid PTEN low patients with G3BP1 aggregating as SGs in CD68+ cells, a finding that was consistent with the observation in our study that PTEN-deficient macrophages tended to more readily assemble SGs with impaired phagocytosis. Our results revealed the unconventional impact of SGs on BMDMs and might provide new perspectives on drug resistance and therapeutic strategies for the treatment of BRCA patients.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-024-02094-0