Dysregulation of cellular signaling in gastric cancer.
The pathogenesis of gastric cancer is complex and related to multiple factors. Dysregulation of intracellular signaling pathways represents a common pathogenic mechanism and may be amenable to drug targeting. Multiple well-established oncogenic pathways, such as those mediated by cell cycle regulators, nuclear factor-kappaB, cyclooxygenase-2 and epidermal growth factor receptor are implicated in gastric carcinogenesis. Emerging evidence also underscores the importance of signaling pathways involved in the developmental process, including transforming growth factor-beta/bone morphogenetic protein signaling, Wnt/beta-catenin signaling, Hedgehog signaling and Notch signaling. Understanding their biological significance will provide a rational basis for drug development. Their relative importance and cross-talk in gastric carcinogenesis, however, are still not completely understood and warrant further investigation.
Wu
William K K
WK
LKS Institute of Health, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, China. wukakei@cuhk.edu.hk
Cho
Chi H
CH
Lee
Chung W
CW
Fan
Daiming
D
Wu
Kaichun
K
Yu
Jun
J
Sung
Joseph J Y
JJ
D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D015289:Leukotrienes / Q000502:physiology; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000502:physiology; D010960:Plasminogen Activators / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes; D016328:NF-kappa B; D010960:Plasminogen Activators; D018719:Erb-b2 Receptor Tyrosine Kinases; D051880:Receptors, Notch; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human