AI Article Synopsis
- Breast cancer (BRCA) is the most common cancer among women, and improving treatment effectiveness is a significant challenge.
- This study explores how loss of the tumour suppressor PTEN in myeloid cells affects anti-tumour immunity, revealing that it leads to increased stress granule assembly, which in turn impairs the immune response.
- The findings suggest that PTEN deficiency in macrophages could contribute to drug resistance in BRCA treatment, indicating potential new strategies for improving therapy outcomes.
Article Abstract
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 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289284 | PMC |
| http://dx.doi.org/10.1038/s41420-024-02094-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Correlation of SNHG7 and BGL3 expression in patients with de novo acute myeloid leukemia; novel insights into lncRNA effect in PI3K signaling context in AML pathogenesis.
Biochem Biophys Rep
December 2024
Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Arak University of Medical Sciences, Arak, Iran.
Background: Acute myeloid leukemia (AML) has been identified as a top priority for discovering a reliable biomarker for treatment improvement and patient outcome prediction due to the heterogeneous nature of AML and the obstacle to find an appropriate treatment strategy for this malignancy. Considering the involvement of long noncoding RNA (lncRNA) SNHG7 and BGL3 found in various cancers, the exact expression pattern of these lncRNAs and their clinical implications in acute myeloid leukemia (AML) continue to be elusive. In order to demonstrate a possible mechanism underlying AML pathogenesis, our goal was to examine BGL3 and SNHG7 lncRNA expressions in PI3K pathway.
View Article and Find Full Text PDFGenome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous () in sensitivity of acute myeloid leukemia to chemotherapy.
J Zhejiang Univ Sci B
August 2024
Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Article Synopsis
- Although advancements in targeted drugs for acute myeloid leukemia (AML) have been made, chemotherapy remains the primary treatment and overall patient survival rates are still low.
- A novel compound, NL101, shows promise in treating AML by inhibiting the growth of leukemia cells, causing DNA damage, and triggering apoptosis through a specific gene's involvement.
- The study suggests that the PTEN gene plays a crucial role in how well AML cells respond to NL101, and combining NL101 with rapamycin could enhance treatment effectiveness.
Myeloid PTEN loss affects the therapeutic response by promoting stress granule assembly and impairing phagocytosis by macrophages in breast cancer.
Cell Death Discov
July 2024
Department of Clinical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Article Synopsis
- Breast cancer (BRCA) is the most common cancer among women, and improving treatment effectiveness is a significant challenge.
- This study explores how loss of the tumour suppressor PTEN in myeloid cells affects anti-tumour immunity, revealing that it leads to increased stress granule assembly, which in turn impairs the immune response.
- The findings suggest that PTEN deficiency in macrophages could contribute to drug resistance in BRCA treatment, indicating potential new strategies for improving therapy outcomes.
The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia.
Pathol Oncol Res
July 2024
Department of Hematology, Szabolcs-Szatmár-Bereg County Teaching Hospital, Nyíregyháza, Hungary.
Signaling pathways of Retinoblastoma (Rb) protein, Akt-kinase, and Erk-kinase (extracellular signal-regulated kinase) have an important role in the pathogenesis of acute myeloid leukemia. Constitutive activation of these proteins by phosphorylation contributes to cell survival by regulation of cell cycle, proliferation and proapoptotic signaling processes. According to previous data phosphorylated forms of these proteins represent a worse outcome for cancer patients.
View Article and Find Full Text PDFA biochemical assessment of apoptosis-inducing impact of Salinomycin in combination with ciprofloxacin on human leukemia KG1-a stem-like cells in the presence and absence of insulin.
Mol Biol Rep
July 2024
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Background: Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!