Understanding the mechanisms that enable cancer cells to metastasize is essential in preventing cancer progression. Here we examine the metabolic adaptations of metastasis-initiating cells (MICs) in female breast cancer and how those shape their metastatic phenotype. We find that endogenous MICs depend on the oxidative tricarboxylic acid cycle and fatty acid usage. Sorting tumor cells based upon solely mitochondrial membrane potential or lipid storage is sufficient at identifying MICs. We further identify that mitochondrially-generated citrate is exported to the cytoplasm to yield acetyl-CoA, and this is crucial to maintaining heightened levels of H3K27ac in MICs. Blocking acetyl-CoA generating pathways or H3K27ac-specific epigenetic writers and readers reduces expression of epithelial-to-mesenchymal related genes, MIC frequency, and metastatic potential. Exogenous supplementation of a short chain carboxylic acid, acetate, increases MIC frequency and metastasis. In patient cohorts, we observe that higher expression of oxidative phosphorylation related genes is associated with reduced distant relapse-free survival. These data demonstrate that MICs specifically and precisely alter their metabolism to efficiently colonize distant organs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625534 | PMC |
| http://dx.doi.org/10.1038/s41467-023-42748-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impact of immunosuppressants on tumor pulmonary metastasis: new insight into transplantation for hepatocellular carcinoma.
Cancer Biol Med
December 2024
Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), School of Clinical Medicine, Hangzhou Medical College, Hangzhou 310014, China.
Pulmonary metastasis is a life-threatening complication for patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). In addition to the common mechanisms underlying tumor metastasis, another inevitable factor is that the application of immunosuppressive agents, including calcineurin inhibitors (CNIs) and rapamycin inhibitors (mTORis), after transplantation could influence tumor recurrence and metastasis. In recent years, several studies have reported that mTORis, unlike CNIs, have the capacity to modulate the tumorigenic landscape post-liver transplantation by targeting metastasis-initiating cells and reshaping the pulmonary microenvironment.
View Article and Find Full Text PDFHybrid Biosilica Nanoparticles for in-vivo Targeted Inhibition of Colorectal Cancer Growth and Label-Free Imaging.
Int J Nanomedicine
November 2024
National Research Council, Institute of Genetics and Biophysics, Naples, 80131, Italy.
Article Synopsis
- The study focuses on metastasis-initiating cells in colorectal cancer (CRC) and explores the relationship between TGF-β signaling and L1CAM, aiming to combat cancer progression and resistance.
- Researchers developed a hybrid nanosystem using gold nanoparticles covered with porous biosilica and modified with L1CAM antibodies, which targets tumor-initiating cells and delivers a TGF-β inhibitor to reduce metastasis.
- Results showed that the nanosystem effectively decreases tumor growth in CRC models, demonstrating its potential for targeted therapy and imaging, paving the way for personalized treatment strategies.
Revelation of comprehensive cell profiling of primary and metastatic tumour ecosystems in oral squamous cell carcinoma by single-cell transcriptomic analysis.
Int J Med Sci
September 2024
College & Hospital of Stomatology, Guangxi Medical University, Nanning 530021, P. R. China.
The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy.
View Article and Find Full Text PDFALDH1A1 as a marker for metastasis initiating cells: A mechanistic insight.
Exp Cell Res
September 2024
Cancer Research, Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thiruvananthapuram, Kerala, 695014, India; Regional Centre for Biotechnology, Faridabad, Haryana 121001, India. Electronic address:
Since metastasis accounts for the majority of cancer morbidity and mortality, attempts are focused to block metastasis and metastasis initiating cellular programs. It is generally believed that hypoxia, reactive oxygen species (ROS) and the dysregulated redox pathways regulate metastasis. Although induction of epithelial to mesenchymal transition (EMT) can initiate cell motility to different sites other than the primary site, the initiation of a secondary tumor at a distant site depends on self-renewal property of cancer stem cell (CSC) property.
View Article and Find Full Text PDFMapping the breast tumor microenvironment: proximity analysis reveals spatial relationships between macrophage subtypes and metastasis-initiating cancer cells.
Oncogene
September 2024
Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Article Synopsis
- Metastasis is a big reason why many people die from cancer, and this study found specific cancer cells that help it spread.
- The researchers looked at how these cancer cells interact with other cells in their environment using a special imaging technique.
- They discovered that the cancer cells that cause metastasis are often found close to certain types of immune and connective tissue cells, which might help them spread even more.
Want 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!