Pathology Graduate Training Program
Name: Weixin Zhou
Cellular and Molecular Pathology (CMP) -
Undergraduate Degree: B.S.
Undergraduate Degree Year: 1997
Undergraduate Institution: Zhongshan University, China
Undergraduate Major: Biochemistry
Academic Status: 5th Year
Graduate Program: Experimental Pathology
Thesis Advisor: Alen Wells, M.D. D.M.S.
Thesis Title/Research Topic: Stat3 In EGF Receptor Mediated Fibroblasts And Human Prostate Cancer Cells Migration And Invasion And Apoptosis
Current Research Description: Growth factor-induced migration is a rate limiting step in tumor invasiveness. The molecules that regulate this cellular behavior would represent novel targets for limiting tumor cell progression. Epidermal growth factor (EGF) receptor (EGFR)-mediated motility, present in both autocrine and paracrine modes in prostate carcinomas, requires de novo transcription to persist over times greater than a few hours. Therefore, we sought the specific signaling pathways that directly alter cellular transcription. We confirmed that STAT3 directly associates with, and is activated by EGFR in DU-145 and PC3 human prostate carcinoma cells in addition to the model NR6 fibroblast cell line. This correlated with electrophoretic motility shift of STAT3-selective oligonucleotides. Inhibition of STAT3 activity by antisense or siRNA down-regulation or expression of a dominant-negative construct limited cell motility as determined by an in vitro wound healing assay and invasiveness through a matrix barrier. The expression of constitutively activated STAT3 did not increase the migration, which indicates that STAT3 is necessary but not sufficient for EGFR-mediated migration. An initial gene array detected a number of candidate operative molecules; the protein levels of both ENA/VASP, a repressor of cell motility, and caspase 3, a nexus of apoptotic signaling, were downregulated by EGF in a STAT3-dependent manner. Preliminary data shows STAT3 is required in EGF induced apoptosis inhibition in two human prostate cancer cell lines. These findings suggest that STAT3 signaling may be a new target for limiting prostate tumor cell invasion and inducing apoptosis.
- LH Qu, A Henbas, YJ Lu, H Zhou, WX Zhou, YQ Zhu, J Zhao, Y Henry, M C Ferrer and J P Bachellerie: Seven novel methylation-guide snoRNAs are processed from a common polycistronic transcript by Rat1p and RNase III in yeast Mol. Cell. Biol. 1999 Feb 19(2): 1144-1158
- YJ Lu, H Zhou, WX Zhou, YQ Zhu and LH Qu: A Novel snoRNA Gene Cluster in Yeast is Transcriped as Polycistronic Pre-snoRNAs Science in China (Series C) 1999 Oct 42(5): 529-537
- YJ Lu, H Zhou, J Zhao and WX Zhou Identification of A Novel Antisense Small Nucleolar RNA form Yeast Acta Scientiarum Naturalium, Zhongshan University 1998 Mar Vol. 37 No. 2 57-60
- H Zhou, LH Qu, YP Du and WX Zhou The identification of a novel methylated nucleoside in Schizosaccharomyces pombe U6 snRNA Chinese Science Bulletin 2000 Vol. 45 No.4, 402-407