| A |
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Adenosine monophosphate kinase (AMPK)
An enzyme that monitors cellular energy status. AMPK is activated in response to low nutrient levels and other metabolic stresses, resulting in inhibition of mTOR and, therefore, the inhibition of protein synthesis. |
Adenosine triphosphate (ATP)
The key transporter of chemical energy within all living cells. In signaling pathways, ATP is used as an energy donor by kinase enzymes that phosphorylate other proteins. |
Akt
One of the most important survival kinases. Akt is involved in regulating cellular metabolism, growth, proliferation, and survival. Also known as protein kinase B (PKB). Akt is downstream from PI3K and upstream from mTOR. |
Angiogenesis
A physiological process involving the formation of new blood vessels from existing vessels. |
Angiopoietin-2
A key angiogenic factor that destabilizes existing capillaries so that new blood vessels can grow from them. |
Apoptosis
Programmed cell death. |
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| B |
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Bioenergetics
A discipline within biochemistry dedicated to the study of energy flow within living systems. |
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| C |
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Clear-cell renal cell carcinoma
A type of renal cell carcinoma arising from the proximal renal tubular epithelial cells. Characterized by cells with abundant clear cytoplasm and an alveolar pattern of growth. Clear-cell renal cell carcinoma comprises 80% of all renal cell carcinomas. |
Constitutive activation
When a receptor or other signaling protein is abnormally activated because it no longer responds to biochemical signals telling it to "turn off." Mutations that cause receptors or other signaling proteins to be constitutively activated are a key cause of many types of cancer. |
Cyclin D1
A key regulatory protein responsible for the transition from the G1 (growth) to the S (synthesis) phase of the cell cycle. |
CXCR4
A chemokine receptor that that enhances metastasis; up-regulated by HIF-1 |
CXCL12
A ligand of the chemokine CXCR4; up-regulated by HIF-1 |
Cyclin-dependent kinases (CDKs)
Key kinases involved in the regulation of the cell cycle. Each one is activated by one or more cyclins. More than 10 cyclin-dependent kinases have been identified to date. |
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| E |
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Epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR)
A growth factor that plays an important role in cell growth, proliferation, and differentiation. The epidermal growth factor receptor is upstream from mTOR. It is a key target in lung, colorectal, and other cancers. |
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| G |
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GLUT1
A glucose transporter that may enable cancer cells to survive better under hypoxic conditions by increasing their ability to produce energy through oxygen-independent mechanisms such as glycolysis; up-regulated by HIF-1. |
Glycolysis
The generation of energy from glucose without requiring oxygen. |
G1-S restriction point
A checkpoint in the cell proliferation process during which the cell assesses whether its DNA is intact and functioning normally before moving into the S (synthesis) phase of the cell cycle. |
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| H |
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HER2
Human epidermal growth factor receptor 2. An important therapeutic target in breast cancer. It is upstream from mTOR. |
Hypoxia
Deprived of an adequate oxygen supply. |
Hypoxia-inducible factor (HIF)/HIF-1α/HIF-1β/HIF-2α
A transcription factor that regulates the expression of more than 60 genes involved in angiogenesis, as well as cell metabolism, proliferation, motility, adhesion, and survival. HIF consists of 2 subunits: HIF-1α and HIF-1β. HIF-1α acts as an oxygen sensor. In normal, well-oxygenated cells, it is immediately inactivated and degraded; under hypoxic conditions, it bonds with HIF-1β and promotes the transcription of the HIF target genes. HIF-2α is an alternate subunit that can also bond with HIF-1β. Overexpression of HIF-1α or HIF-2α has been associated with a number of cancers. |
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| I |
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Insulin-like growth factor-1 (IGF-1)/Insulin-like growth factor-1 receptor (IGF-1R)
A growth factor that plays an important role in cell proliferation and survival. The IGF-1 receptor is highly overexpressed in many malignant tissues, including neuroendocrine tumors and renal cell carcinoma. It is upstream from mTOR. |
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| K |
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Kinase
A type of enzyme that activates or inactivates one or more specific substrates (often other enzymes) by phosphorylating (transferring phosphate groups to) them. |
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| L |
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Lymphangiogenesis
A physiological process involving the formation of lymphatic vessels from pre-existing lymphatic vessels. Has been shown to play a causal role in lymphatic metastasis in cancer. |
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| M |
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Mammalian target of rapamycin (mTOR)
A kinase protein found predominantly in the cytoplasm of the cell that acts as a central regulator of many biological processes that are essential for cell proliferation, angiogenesis, and cell metabolism. mTOR is deregulated in many types of cancer. |
MDR-1
An oncogene that encodes for the expression of P-glycoprotein (Pgp), a membrane transporter that confers multidrug resistance to chemotherapy; up-regulated by HIF-1. |
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| N |
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Neuroendocrine tumor (NET)
Rare tumors that originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. |
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| O |
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Oxidative phosphorylation
The generation of energy utilizing oxygen. Significantly more efficient than glycolysis. |
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| P |
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p21
A cyclin-dependent kinase inhibitor that arrests the cell cycle in G1 phase so that DNA repair can take place. Also known as CDKN1A. |
Phosphatase and tensin homolog (PTEN)
A phosphatase enzyme that acts as a tumor suppressor. Defective PTEN plays a role in breast, prostate, neuroendocrine, brain, thyroid, endometrial, and other cancers. It is upstream from mTOR. |
Phosphoinositide 3-kinase (PI3K)
An oncoprotein that phosphorylates lipids, resulting in their recruitment to the cell membrane. It is upstream from mTOR. |
Platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR)
A growth factor that plays a key role in cell growth, proliferation, and migration as well as angiogenesis. An important therapeutic target in a number of cancers. The platelet-derived growth factor receptor is upstream from mTOR. |
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| R |
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Receptor tyrosine kinase (RTK)
Proteins that form cell surface receptors for growth factors, cytokines, and hormones. RTKs are key regulators of many normal cellular processes but also play a critical role in the development and progression of many types of cancer |
Ribosome
Structures of RNA and proteins found in the cytoplasm of all cells that are the site of translation—the first step in the assembly of proteins from individual amino acids. |
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| S |
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Signaling pathway
An ordered sequence of biochemical reactions carried out within a cell that is orchestrated by specific enzymes. Enables the cell to perform key functions and respond to its environment. Also known as a signal transduction pathway. |
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| T |
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Transcription factor
A protein that binds to specific regions of DNA and regulates gene transcription. Some transcription factors upregulate transcription of particular genes while others downregulate transcription. |
Transforming growth factor (TGF)/TGF-α/TGF-β
Two families of growth factors (α and β) capable of inducing malignant transformation. |
Translational machinery
The ribosomes and other components of the cell responsible for synthesizing proteins from individual amino acids. |
Tuberous sclerosis complex/TSC1/TSC2
A complex of 2 proteins, TSC1 (hamartin) and TSC2 (tuberin), that lie downstream from AKT and upstream from mTOR. When activated, the tuberous sclerosis complex acts as an inhibitor of mTOR activation. Defective TSC, which occurs in certain cancers, leads to abnormal mTOR activation. |
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Vascular endothelial growth factors (VEGFs)/Vascular endothelial growth factor receptors (VEGFRs)
A family of growth factors and their receptors that play a primary role in both angiogenesis and lymphangiogenesis by attracting and organizing vascular endothelial cells. VEGFs and VEGFRs are key therapeutic targets in a number of cancers. |
Von Hippel-Lindau (VHL) protein
A tumor suppressor protein that facilitates the rapid degradation of HIF in normal, well-oxygenated cells. Defective or missing VHL protein is a key cause of renal cell carcinoma, pancreatic cancer, and neuroendocrine tumors. |
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