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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis is the main cause of cancer-related deaths and there are limited therapeutic options for patients with metastatic disease. The identification and testing of novel therapeutic targets that will facilitate the development of better treatments for metastatic disease requires preclinical in vivo models. Demonstrated here is a syngeneic mouse model for assaying breast cancer metastatic colonization and subsequent growth. Metastatic cancer cells are stably transduced with viral vectors encoding firefly luciferase and ZsGreen proteins. Candidate genes are then stably manipulated in luciferase/ZsGreen-expressing cancer cells and then the cells are injected into mice via the lateral tail vein to assay metastatic colonization and growth. An in vivo imaging device is then used to measure the bioluminescence or fluorescence of the tumor cells in the living animals to quantify changes in metastatic burden over time. The expression of the fluorescent protein allows the number and size of metastases in the lungs to be quantified at the end of the experiment without the need for sectioning or histological staining. This approach offers a relatively quick and easy way to test the role of candidate genes in metastatic colonization and growth, and provides a great deal more information than traditional tail vein metastasis assays. Using this approach, we show that simultaneous knockdown of Yes associated protein (YAP) and transcriptional co-activator with a PDZ-binding motif (TAZ) in breast cancer cells leads to reduced metastatic burden in the lungs and that this reduced burden is the result of significantly impaired metastatic colonization and reduced growth of metastases.
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PMID:Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs. 3190 24

Disseminated metastatic cancer cells represent one of the most relevant causes of disease relapse and associated death for cancer patients, and a therapeutic target of the highest priority. Still, our understanding of how disseminated cancer cells survive in the foreign metastatic environment, and eventually cause metastatic outgrowth, remains rather limited. In this review we focus on the cell microenvironment as a key regulator of cell behavior at the metastatic site, and especially on the mechanical properties of the extracellular matrix and associated integrin signaling. We discuss available evidence pointing to a pervasive role of extracellular matrix (ECM) mechanical properties in regulating cancer cell proliferation and survival after dissemination, and propose that this might represent an important bottleneck for cells invading and establishing into a novel tissue. We point to the known molecular players, how these might contribute to modulate the mechanical properties of the metastatic environment, and the response of cells to these cues. Finally, we propose that emerging knowledge on the physical interaction of disseminated metastatic cells and on the downstream mechanotransduction pathways, including YAP/TAZ (Yes-associated protein-1 and WW-domain transcription activator 1) and MRTFs (Myocardin-related transcription factors), may help to identify novel approaches for therapy.
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PMID:Mechanical Forces as Determinants of Disseminated Metastatic Cell Fate. 3196 20

Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) are the downstream effectors of the Hippo signaling pathway that play a crucial role in various aspects of cancer progression including metastasis. Metastasis is the multistep process of disseminating cancer cells in a body and responsible for the majority of cancer-related death. Emerging evidence has shown that cancer cells reprogram their metabolism to gain proliferation, invasion, migration, and anti-apoptotic abilities and adapt to various environment during metastasis. Moreover, it has increasingly been recognized that YAP/TAZ regulates cellular metabolism that is associated with the phenotypic changes, and recent studies suggest that the YAP/TAZ-mediated metabolic alterations contribute to metastasis. In this review, we will introduce the latest knowledge of YAP/TAZ regulation and function in cancer metastasis and metabolism, and discuss possible links between the YAP/TAZ-mediated metabolic reprogramming and metastasis.
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PMID:A Potential Role of YAP/TAZ in the Interplay Between Metastasis and Metabolic Alterations. 3259 54

The physical cues in the extracellular environment play important roles in cancer cell metastasis. However, how metastatic cancer cells respond to the diverse mechanical environments of metastatic sites is not fully understood. Here, substrates with different mechanical properties are prepared to simulate the extracellular mechanical environment of various human tissues. The prostate cancer (PC) cells derived from different cancer metastasis sites show heterogeneity in mechanical response. This heterogeneity mediates two distinct metastasis patterns. High stiffness promotes individual cell migration and proliferation by inducing Yes-associated protein and tafazzin (YAP/TAZ) nuclear localization in bone metastasis-derived cells, whereas low stiffness promotes cell migration and proliferation by inducing lymphatic metastasis-derived cells to form clusters characterized by high expression of CD44. The different metastasis patterns induced by the mechanical properties of the extracellular environment are crucial in the development of PC.
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PMID:Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns. 3277 49

Breast cancer is the most commonly diagnosed cancer among women. Although routine and targeted therapies have improved the survival rate, there are still considerable challenges in the treatment of breast cancer. Metastasis is the leading cause of death in patients diagnosed with breast cancer. Yes-associated protein (YAP) and/or PDZ binding motif (TAZ) are usually abnormally activated in breast cancer leading to a variety of effects on tumour promotion, such as epithelial-mesenchymal transition, cancer stem cell production and drug-resistance. The abnormal activation of YAP/TAZ can affect metastasis-related processes and promote cancer progression and metastasis by interacting with some metastasis-related factors and pathways. In this article, we summarise the evidence that YAP/TAZ regulates breast cancer metastasis, its post-translational modification mechanisms, and the latest advances in the treatment of YAP/TAZ-related breast cancer metastasis, besides providing a new strategy of YAP/TAZ-based treatment of human breast cancer.
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PMID:Transcriptional co-activators YAP/TAZ: Potential therapeutic targets for metastatic breast cancer. 3318 66


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