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Signaling pathways downstream to receptor tyrosine kinases:targets for cancer treatment

Journal of Cancer Metastasis and Treatment 2020年第1期6卷 556-574页

作者： Emma Cordover Audrey Minden Susan Lehman Cullman Laboratory for Cancer Research Department of Chemical BiologyErnest Mario School of PharmacyRutgersThe State University of New JerseyPiscatawayNJ 08854USA

Mammalian cells have the ability to respond to a myriad of diverse extracellular stimuli that modulate cell function.This often involves ligands binding to cell surface receptors and subsequent activation of intracellular signaling pathways.These pathways can lead to changes in gene expression patterns that in turn regulate cell growth,differentiation,migration,and function.One important type of cell surface receptor is the receptor tyrosine kinase(RTK).In response to in response to ligand binding,RTKs dimerize,then trans-phosphorylate each other,leading to activation of downstream pathways.While the signaling proteins in these pathways are important for normal cell growth control,when improperly regulated they can lead to uncontrolled growth and sometimes cancer.For this reason,they are often considered to be good candidates for drug targets for chemotherapeutic drugs.RTKs can activate multiple different signaling pathways.Some of the signaling proteins in these pathways can have crosstalk with other RTK activated pathways,and some of them can be activated by multiple mechanisms in addition to activation by RTKs.While there is a wide array of different signaling proteins and pathways activated by RTKs,in this review we will discuss components of several key pathways including the MAPK pathway,the Her2/Neu pathway,mTOR,and Pak kinases.We provide an overview of the roles for these pathways in cell signaling and discuss how different components of these pathways are being considered as targets for cancer treatment.

关键词： receptor tyrosine kinases signaling pathways targeted cancer therapeutics oncogenes cell signaling

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Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

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Chinese Medical Journal 2007年第9期120卷 743-748页

作者： ZHANG Yu-hua WEI Wei XU Hao WANG Yan-yan WU Wen-xi Department of Genaral Surgery First Affiliated Hospital of Nanjing Medical University. Nanjing 210029 China Immunology Research division Department of pathology Brigham Women＇s Hospital Boston MA 02115 USA

Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells. Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA. The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells. Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial arowth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT sianalina Pathways.

关键词： hepatocyte growth factor/scatter factor vascular endothelial growth factor signaling pathway receptor tyrosine kinases colorectal carcinoma

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