Signal transduction in human pancreatic cancer: roles of transforming growth factor beta, somatostatin receptors, and other signal intermediates.
Pancreatic cancer is a devastating disease because of the lack of early detection markers and effective treatments. It is the fourth leading cause of cancer-related death in western countries, including the United States. The mechanisms of pancreatic cancer progression remain unknown. Transforming growth factor beta (TGF-beta), a multifunctional cytokine, regulates cell growth and differentiation in healthy tissues, yet fails to do so in pancreatic cancer. Alterations of the TGF-beta and TGF-beta receptor/Smad signal transduction pathway have been implicated in pancreatic cancer. Furthermore, both the TGF-beta receptor and Smad proteins interact with a variety of cellular signal pathways, such as the somatostatin receptors (SSTRs), ERK1/2, and Wnt signal transduction cascades. This suggests that pancreatic cancer is a multi-gene-controlled malignancy and that effective treatments for pancreatic cancer should be aimed at multiple targets. In this review, we summarized the major signal intermediates involved in pancreatic cancer signal transduction pathways and specifically discussed how alterations in the regulatory functions of TGF-beta and Smad proteins allow for pancreatic carcinogenesis.
Li
Min
M
Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77021, USA. minli@bcm.tmc.edu
Becnel
Lauren S
LS
Li
Wei
W
Fisher
William E
WE
Chen
Changyi
C
Yao
Qizhi
Q
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D017481:Receptors, Somatostatin; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta