Abstract

EGF-induced signaling and increased beta-catenin transactivation have been reported separately to correlate with tumor formation and development. However, the exact relationship between EGF-induced signaling and increased beta-catenin transactivation is not clear. Our preliminary data show that EGF treatment disrupts cell-cell junctions of tumor cells overexpressing EGFR and increases beta-catenin transactivation. Moreover, EGF-induced beta-catenin transactivation is regulated through caveolin-1- and Ras/Raf/ERK-dependent pathways. ERK MAP kinase binds to beta-catenin, leading to our exploration into the mechanism of EGF-induced beta-catenin transactivation and its role in the development of human cancers that have aberrantly overexpress EGFR.
In Aim 1, we will analyze the relationship between ERK and beta-catenin in response to EGF treatment and the role of this relationship in beta-catenin nuclear translocation and transactivation.
Aim 2 focuses on understanding the mechanism of ERK-independent but caveolin-1-dependent regulation of beta-catenin transactivation and the mechanism of beta-catenin endocytosis in response to EGF stimulation.
In Aim 3, we plan to determine the role of beta-catenin transactivation in EGFR-related tumor growth and metastasis. Understanding the interplay between EGFR and Wnt signaling components will provide an important basis for understanding tumor cell invasion and metastasis, which may provide novel targets and approaches for developing more effective cancer therapies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA109035-02
Application #
7101110
Study Section
Tumor Cell Biology Study Section (TCB)
Program Officer
Woodhouse, Elizabeth
Project Start
2005-08-01
Project End
2010-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$262,095
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Neurology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Qian, Xu; Li, Xinjian; Tan, Lin et al. (2018) Conversion of PRPS Hexamer to Monomer by AMPK-Mediated Phosphorylation Inhibits Nucleotide Synthesis in Response to Energy Stress. Cancer Discov 8:94-107
Yang, Weiwei; Xia, Yan; Cao, Yu et al. (2018) EGFR-Induced and PKC? Monoubiquitylation-Dependent NF-?B Activation Upregulates PKM2 Expression and Promotes Tumorigenesis. Mol Cell 69:347
Lee, Jong-Ho; Liu, Rui; Li, Jing et al. (2018) EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation. Mol Cell 70:197-210.e7
Lu, Zhimin; Hunter, Tony (2018) Metabolic Kinases Moonlighting as Protein Kinases. Trends Biochem Sci 43:301-310
Wang, Yugang; Guo, Yusong R; Liu, Ke et al. (2017) KAT2A coupled with the ?-KGDH complex acts as a histone H3 succinyltransferase. Nature 552:273-277
Li, Xinjian; Yu, Willie; Qian, Xu et al. (2017) Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy. Mol Cell 66:684-697.e9
Qian, Xu; Li, Xinjian; Cai, Qingsong et al. (2017) Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy. Mol Cell 65:917-931.e6
Xia, Yan; Yang, Weiwei; Fa, Ming et al. (2017) RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis. J Exp Med 214:1843-1855
Lee, Jong-Ho; Liu, Rui; Li, Jing et al. (2017) Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis. Nat Commun 8:949
Li, Xinjian; Qian, Xu; Peng, Li-Xia et al. (2016) A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation. Nat Cell Biol 18:561-71

Showing the most recent 10 out of 44 publications