Proc Natl Acad Sci U S A 2012 Aug 6;109(34):13787-92. Epub 2012 Aug 6.
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
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Oncogene 2012 Nov 23;31(47):4935-45. Epub 2012 Jan 23.
Department of Biology, University of North Carolina, Charlotte, NC 28223, USA.
Pancreatic ductal adenocarcinoma (PDA) has one of the worst prognoses of all cancers. Mucin 1 (MUC1), a transmembrane mucin glycoprotein, is a key modulator of several signaling pathways that affect oncogenesis, motility and metastasis. Its expression is known to be associated with poor prognosis in patients. Read More
Cancer Cell 2017 07;32(1):71-87.e7
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address:
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. Read More
J Biol Chem 2007 Jan 13;282(1):257-66. Epub 2006 Nov 13.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Resistance of carcinoma cells to hypoxic stress is of importance to the growth of solid tumors. The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed by most human carcinomas; however, there is no known relationship between MUC1 and the hypoxic stress response. The present work has demonstrated that MUC1 attenuates activation of hypoxia-inducible factor-1alpha (HIF-1alpha), a regulator of gene transcription in the response of cells to hypoxic stress. Read More
Int J Cancer 2014 Jun 30;134(12):2798-807. Epub 2014 Jan 30.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Aberrant glucose metabolism characterized by high levels of glycolysis, even in the presence of oxygen, is an important hallmark of cancer. This metabolic reprogramming referred to as the Warburg effect is essential to the survival of tumor cells and provides them with substrates required for biomass generation. Molecular mechanisms responsible for this shift in glucose metabolism remain elusive. Read More