Breast cancer-secreted miR-122 reprograms glucose metabolism in pre-metastatic niche to promote metastasis

By M. Fong, Weiying Zhou, Liang Liu, A. Alontaga, M. Chandra, Jonathan Ashby, A. Chow, S. O’Connor, Shasha Li, Andrew R. Chin and 15 more. Nature Cell Biology, 2015

1,061 citations recorded by the source corpus.

Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients, and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the premetastatic niche. Mechanistically, cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that, by modifying glucose utilization by recipient premetastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/458ff48e70c32a11bacff60a05c654634bfb27a2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Robert Blelloch
2. Xuetao Cao
3. Yan Luo
4. Ben Wang
5. Lin Zhang
6. Yang Liu
7. Dihua Yu
8. Jerrold M. Olefsky

In Molecular Biology

1. Amanda Birmingham
2. Robert Blelloch
3. Xuetao Cao
4. H. Peinado
5. Yan Luo
6. Ben Wang
7. Lin Zhang
8. Yang Liu

Citations in the corpus

• Characteristics and Significance of the Pre-metastatic Niche. (2016, background): “…reprograms glucose metabolism in the niche; facilitates metastasis by increasing nutrient availability in the niche breast carcinoma (MDA-MB-231) Fong et al. (2015) tumor large oncosome miR-1227 undetermined induces the migration of CAFs to promote tumor metastasis prostate cancer (DU145, PC3)…”
• Exosome-Based Cell-Cell Communication in the Tumor Microenvironment (2018, background): “…protein (AHNAK) Differentiation of fibroblast into CAF Silva et al., 2016 Metabolic Environment miR-122 Suppression of glucose uptake Fong et al., 2015 Establishment of Pre-metastatic niches hTERT mRNA Increased fibroblast proliferation and lifespan Gutkin et al., 2016 CD151,…”
• Exosomes in cancer development, metastasis, and immunity (2019, background): “Glucose uptake by niche cells such as lung fibroblasts and brain astrocytes were suppressed by miR-122 through the downregulation of the glycolytic enzyme pyruvate kinase, thereby increasing nutrient availability for metastatic cancer cell growth [106].”
• Tumor microenvironment complexity and therapeutic implications at a glance (2020, background): “Mechanistically, miR-122 downregulate the glycolytic enzyme pyruvate kinase and restores glucose uptake by lungs and brain and lessen disease progression [177] .”
• Exosome Theranostics: Biology and Translational Medicine (2018, background): “Interestingly, an amazing piece of work showed that cancer cell-derived exosomes containing miR-122 could suppress glucose uptake in non-tumor cells in the premetastatic niche, suggesting that the systemic energy metabolism can be reprogramed by exosomes and that disease progression can be facilitat”
• Exosomes in cancer: small particle, big player (2015, background): “miR-122 Breast cancer cells Lung fibroblasts, brain astrocytes, and neurons Reprograms systemic energy metabolism and facilitates metastasis [113]”
• Tumor-derived exosomes and their role in cancer progression (2016, background): “Nevertheless, in instances when tumor antigen-carrying exosomes are known to bind to therapeutic antibodies and interfere with therapy, as is the case, for example with CD20+ exosomes produced by B-cell lymphoma cells which bind to rituximab [45], removal of exosomes from plasma using a well-known p”
• Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory (2019, background): “, 2014), and, even, establish pre-metastatic niches (Fong et al., 2015; Hoshino et al., 2015).”
• Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity. (2017, positive): “Evidence also exists that these Exos can be taken up into neighboring or distant cell types to modulate the function of recipient cells (Bang et al., 2014; Costa-Silva et al., 2015; Fong et al., 2015; Zhang et al., 2015b).”