Dr. Keping Xie
The University of Texas MD Anderson Cancer Center
Department of GI Medical Oncology
Department of Cancer Biology
- Cancer metastasis
- Gene regulation
- Molecular diagnosis and therapy
Metastatic pancreatic adenocarcinoma is a lethal disease. Using molecular and cell biology techniques coupled with human specimens and animal models, we have continued to investigate the molecular mechanisms governing pancreatic cancer metastasis, with a focus on the regulation and interplay of multiple transcription factors such as AP-1, NF-kB, Sp1, and Stat3. Abnormal activation of these factors leads to aberrant expression of multiple metastasis-related proteins such as inducible nitric oxide synthase (iNOS), interkeukin-8 (IL-8) and vascular endothelial growth factor (VEGF), which confer a tremendous growth advantage to metastatic pancreatic cancer cells. There are two major pathways leading to overactivation of these transcription factors. One mechanism relates to the genetic mutations of oncogenes and/or suppressor genes, such as Ras and p53, resulting in constitutive activation of the transcription factors. This may be especially true in the early stage of pancreatic cancer growth. In the latter stage of pancreatic cancer development, however, notable "stress factors" such as hypoxia, acidosis and free radicals that are often seen in the tumor microenvironment further upregulates those metastasis-related proteins through overactivating the transcription factors. Therefore, at advanced stages, uncontrolled tumor growth and the consequent development of a stress environment may enhance tumor angiogenesis, growth and metastasis. Understanding the expression and regulation of these molecules may shed more light on the biology of pancreatic cancer metastasis, as well as suggest new preventive and therapeutic approaches.
Tutorials in my laboratory include work on cell lines, animal model and as surgical specimens from human gastrointestinal cancer. A tutorial in my laboratory would provide experience with cell culture, animal models, and various basic and advanced molecular biology in gene expression and regulation of tumor angiogenesis and metastasis.
Wei D, Wang L, Kanai M, Jia Z, Le X, Li Q, Wang H, and Xie K. Altered Expression of KLF4a Promotes Cell Cycle Progression and Is Associated with Poor Prognoses in Patients with Pancreatic Cancer. Gastroenterology. 139:2135-45, 2010.
Jia Z, Gao Y, Wang L, Li Q, Zhang J, Le X, Wei D, Yao JC, Chang DZ, Huang S, and Xie K. Treatment with Combination of Mithramycin A and Tolfenamic Acid Promotes Degradation of Sp1 Protein and Synergistic Antitumor Activity in Pancreatic Cancer. Cancer Res. 2010 Feb 1;70(3):1111-9.
Li Q, Zhang N, Jia Z, Le X, Dai B, Wei D, Huang S, Tan D, and Xie K. The Critical Role for and Regulation of Expression of the Transcription Factor FoxM1 in Human Gastric Cancer Angiogenesis and Progression. Cancer Res. 69:501-9, 2009.
Zheng Y, Xia Y, Hawke D, Halle M, Tremblay ML, Gao X, Zhou XZ, Aldape K, Cobb MH, Xie K, He J, Lu Z. FAK phosphorylation by ERK primes ras-induced tyrosine dephosphorylation of FAK mediated by PIN1 and PTP-PEST. Mol Cell. 35(1):11-25, 2009.
Le X, Wei D, Huang S, Lancaster JR Jr, Xie K. Nitric oxide synthase II suppresses the growth and metastasis of human cancer regardless of its up-regulation of protumor factors. Proc Natl Acad Sci USA. 2005;102 8758-63.
Xie K. and Abbruzzese JL. Developmental biology informs cancer: The emerging role of the hedgehog signaling pathway in upper gastrointestinal cancers. Cancer Cell, 4(4): 5-7, 2003
Program in Cancer Biology