开题报告内容：（包括拟研究或解决的问题、采用的研究手段及文献综述，不少于2000字）
1.Background
(1) Na⁺/K⁺-ATPase
Na⁺/K⁺-ATPase (sodium-potassium adenosine triphosphatase, also known as the Na⁺/K⁺ pump or sodium–potassium pump) is an enzyme (an electrogenic transmembrane ATPase) found in the plasma membrane of all animal cells. It was discovered in 1957 by the Danish scientist Jens Christian Skou. It performs several functions in cell physiology. The Na /K -ATPase helps maintain resting potential, affects transport, and regulates cellular volume.[1] It also functions as a signal transducer/integrator to regulate the MAPK pathway, ROS, as well as intracellular calcium. In fact, all cells expend a large fraction of the ATP they produce (typically 30% and up to 70% in nerve cells) to maintain their required cytosolic Na and K concentrations.
Within the last decade, many independent labs have demonstrated that, in addition to the classical ion transporting, this membrane protein can also relay extracellular ouabain-binding signaling into the cell through regulation of protein tyrosine phosphorylation. The downstream signaling occurs through protein phosphorylation events including activation of the mitogen-activated protein kinase (MAPK) signal cascades, mitochondrial reactive oxygen species (ROS) production, as well as activation of phospholipase C (PLC) and inositol triphosphate (IP3) receptor (IP3R) in different intracellular compartments.[2]
(2) Src kinase
Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Src family kinases interact with many cellular cytosolic, nuclear and membrane proteins, modifying these proteins by phosphorylation of tyrosine residues. A number of substrates have been discovered for these enzymes.[3][4][5] Deregulation, including constitutive activation or over expression, may contribute to the progression of cellular transformation and oncogenic activity.[6]
Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src or simply c-Src , is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. This protein phosphorylates specific tyrosine residues in other proteins.
An elevated level of activity of c-Src tyrosine kinase is suggested to be linked to cancer progression by promoting other signals.[7] This proto-oncogene may play a role in the regulation of embryonic development and cell growth. When src is activated, it promotes survival, angiogenesis, proliferation and invasion pathways in cancer. It also regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion,[8][9] and regulates matrix metalloproteinase-9 activity after intracerebral hemorrhage.[10]
The activation of the c-Src pathway has been observed in about 50% of tumors from colon, liver, lung, breast and the pancreas.[11] Since the activation of c-Src leads to the promotion of survival, angiogenesis, proliferation and invasion pathways, the aberrant growth of tumors in cancers is observed. Increased activity or the overexpression of the c-Src leading to the constant activation of the c-Src which is often observed in various types of cancer.
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