An oncogene is a gene that has the potential to cause cancer. In tumor cells,these genes are often mutated,or expressed at high levels.
Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on that same cell,leading to changes in the cell. This can be contrasted with paracrine signaling,intracrine signaling,or classical endocrine signaling.
A mitogen-activated protein kinase is a type of protein kinase that is specific to the amino acids serine and threonine. MAPKs are involved in directing cellular responses to a diverse array of stimuli,such as mitogens,osmotic stress,heat shock and proinflammatory cytokines. They regulate cell functions including proliferation,gene expression,differentiation,mitosis,cell survival,and apoptosis.
A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division,or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis,typically via a mitogen. The mechanism of action of a mitogen is that it triggers signal transduction pathways involving mitogen-activated protein kinase (MAPK),leading to mitosis.
The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion,and gain migratory and invasive properties to become mesenchymal stem cells;these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing,in organ fibrosis and in the initiation of metastasis in cancer progression.
Mitogen Activated Protein (MAP) kinase kinase kinase is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently,MAP kinase kinase activates MAP kinase. Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. MAPKKKs are stimulated by a large range of stimuli,primarily environmental and intracellular stressors. MAPKKK is responsible for various cell functions such as cell proliferation,cell differentiation,and apoptosis. The duration and intensity of signals determine which pathway ensues. Additionally,the use of protein scaffolds helps to place the MAPKKK in close proximity with its substrate to allow for a reaction. Lastly,because MAPKKK is involved in a series of several pathways,it has been used as a therapeutic target for cancer,amyloidosis,and neurodegenerative diseases. In humans,there are at least 19 genes which encode MAP kinase kinase kinases:
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib,the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).
The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.
In molecular biology,extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis,mitosis,and postmitotic functions in differentiated cells. Many different stimuli,including growth factors,cytokines,virus infection,ligands for heterotrimeric G protein-coupled receptors,transforming agents,and carcinogens,activate the ERK pathway.
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli,such as cytokines,ultraviolet irradiation,heat shock,and osmotic shock,and are involved in cell differentiation,apoptosis and autophagy. Persistent activation of the p38 MAPK pathway in muscle satellite cells due to ageing,impairs muscle regeneration.
RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. The mouse sarcoma virus 3611 contains a RAF kinase-related oncogene that enhances fibrosarcoma induction. RAF is an acronym for Rapidly Accelerated Fibrosarcoma.
The ErbB family of proteins contains four receptor tyrosine kinases,structurally related to the epidermal growth factor receptor (EGFR),its first discovered member. In humans,the family includes Her1,Her2 (ErbB2),Her3 (ErbB3),and Her4 (ErbB4). The gene symbol,ErbB,is derived from the name of a viral oncogene to which these receptors are homologous:erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases,such as multiple sclerosis and Alzheimer's disease,while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor.
Mitogen-activated protein kinase 14,also called p38-α,is an enzyme that in humans is encoded by the MAPK14 gene.
ETS Like-1 protein Elk-1 is a protein that in humans is encoded by the ELK1. Elk-1 functions as a transcription activator. It is classified as a ternary complex factor (TCF),a subclass of the ETS family,which is characterized by a common protein domain that regulates DNA binding to target sequences. Elk1 plays important roles in various contexts,including long-term memory formation,drug addiction,Alzheimer's disease,Down syndrome,breast cancer,and depression.
Mitogen-activated protein kinase kinase kinase 3 is an enzyme that in humans is encoded by the MAP3K3 gene,which is located on the long arm of chromosome 17 (17q23.3).
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.
Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 is an enzyme that in humans is encoded by the MAP3K2 gene.
Mitogen-activated protein kinase 4 is an enzyme that in humans is encoded by the MAPK4 gene.
Cédric Blanpain is a Belgian researcher in the field of stem cells. He is a tenured professor of developmental biology and genetics at UniversitéLibre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine. He was one of the first researchers in the world to use cell lineage tracing in cancer research and he showed for the first time the existence of cancer stem cells in solid tumors in vivo. He was selected by Nature as one of 10 People who mattered most in 2012 and he received the outstanding young investigator award of the International Society for Stem Cell Research.
Channing Joseph Der is an American scientist and educator,and Sarah Graham Kenan Distinguished Professor of Pharmacology,at UNC Lineberger Comprehensive Cancer Center. Der is a Fellow of the American Association for the Advancement of Science,He is recognized for his work with the Ras oncoprotein and its role in human oncogenesis.
