Esophageal carcinoma is one of the leading causes of death
in Taiwan. The combination of chemotherapeutic agents with
radiotherapy enhance the therapeutic efficacy by ablation the
survival mechanism, i.e. cause massive apoptosis, of
esophageal carcinoma. However, survival signals, i.e.
production of IGF-1 and EGF in esophageal carcinoma cells,
cause the cancer cells to escape from apoptosis. We are
interested in investigating which signaling pathway is
responsible for the IGF-1R and EGFR survival signal in
esophageal carcinoma, by using various chemical signaling
blockers, dominant negative mutants, and shRNA to narrow down
the IGF-1 and EGF-mediated survival signal in esophageal
carcinoma. The identified pathway will be used as a template
to address which signaling components are important for IGF-1R
and EGFR induced survival signals in esophageal carcinoma.
Recently, we focus on two IGF-1 regulated anti-apoptosis
molecules, aurora A, survivin and XIAP. The roles of the two
genes in IGF-1R mediated survival pathway are under
Cleft lip/palate is one of the most common congenital
diseases in Taiwan, and van der Woude syndrome is the most
important syndrome in cleft lip/palate. The mutation of IRF6
gene causes the van der Woude syndrome, thus IRF6 is a good
candidate gene for studying the mechanisms of formation of
cleft lip/palate. We try to understand the molecular
mechanisms of IRF6 on the palate shelves fusion by organ
culture and knockout mouse. We try to identify the target
genes regulated by IRF6 in palate epithelial cells during
palate formation. Our goal is to understand the molecular
mechanism of mutated IRF6 on the formation of cleft palate
during the palate shelves fusion and therefore lay a good
foundation for possible therapeutic intervention and
prevention of cleft palate in the high-risk group.
1. Ke CY, Xiao WL, Chen CM, Lo LJ*, Wong
FH*. IRF6 is the mediator of TGFβ3 during regulation of
the epithelial mesenchymal transition and palatal fusion. Sci.
Rep. 5, 12791; doi: 10.1038/srep12791, 2015.
2. David-Paloyo FP, Yang X, Lin JL,
Wong FH*, Wu-Chou YH, Lo LJ. Lower Lip Pits: Van der
Woude or Kabuki Syndrome? Cleft Palate Craniofac J.
51(6):729-34, doi: 10.1597/12-258, 2014.
Juan HC, Tsai HT, Chang PH, Huang F CY, Hu C, Wong
FH. Insulin-like growth factor 1 mediates
5-fluorouracil chemoresistance in esophageal carcinoma cells
through increasing survivin stability. Apoptosis: DOI:
Wong FH, Huang F C-Y, Su
LJ, Wu YC, Lin YS, Hsia JY, Tsai HT, Lee SA, Lin CH, Liang SC,
Lai JM, Yen CC. Combination of microarray profiling and
protein-protein interaction databases delineates the minimal
discriminators as a metastasis network for esophageal squamous
cell carcinoma. Int J Oncology 34: 117-128, 2009.
Chou WC, Wang HC, Wong FH,
Ding SL, Wu PE, Shieh SY, Shen CY. Chk2-dependent
phosphorylation of XRCC1 in the DNA damage response promotes
base excision repair. EMBO 27: 3140–3150, 2008
Chau GY, Lee A FY, Tsay SH, Ke YR, Kao HL, Wong
FH, Tsou AP, Chau YP. Clinicopathological significance
of survivin expression in patients with hepatocellular
carcinoma. Histopathology 51:204-218, 2007.
Lin YS*, Su LJ*, Yu R. CT*, Wong
FH*, Yeh HH, Chen SL, Wu JC, Lin WJ, Shiue YL, Liu HS,
Hsu SL , Lai JM, Huang F CY. Gene Expression Profiles of the
Aurora Family Kinases. Gene expression 13:15-26, 2006.
Chang JL, Chen TH, Wang CF, Chiang YH, Huang YL, Wong
FH, Chou CK, Chen CM. Borealin/Dasra B is a cell
cycle-regulated chromosomal passenger protein and its nuclear
accumulation is linked to poor prognosis for human gastric
cancer. Exp Cell Res. 312: 962-973, 2006.
Chang JT, Wong FH, Liao
CT, Chen IH, Wang HM, Cheng AJ. Enzyme immunoassay for serum
autoantibody to survivin and its findings in head-and-neck
cancer patients. Clin Chem. 50(7):1261-1264, 2004.
Leu CM, Wong FH, Chang
C, and Hu C. Interleukin-6 acts as an anti-apoptotic factor in
human esophageal carcinoma cells through the activation of both
STAT3 and mitogen-activated protein kinase pathways. Oncogene
22: 7809-7818, 2003.
Liu YC, Leu CM, Wong FH,
Fong WS, Chen SC, Chang C, and Hu C. Autocrine stimulation by
insulin-like growth factor I is involved in the growth,
tumorigenicity, and chemoresistance of human esophageal
carcinoma cells. J. Biochem. Sci. 9: 665-674, 2002.
Yu CC, Wong FH, Lo LJ,
Chen YR. Hereditary cleft lip/palate and Wilms tumor: a rare
association. Cleft Palate-Craniofacial Journal 39(3): 376-379,
Wong FH, Hu C, Chiu JH,
Huang BS, Chien KY, Chang JP, Lin PJ, and Chang C. Expression of
multiple oncogenes in human esophageal carcinomas. Cancer
Investigation 12:121-131, 1994.
Chen SC, Chou CK, Wong FH,
Chang C, and Hu C. Overexpression of epidermal growth factor and
insulin-like growth factor-I receptors and autocrine stimulation
in human esophageal carcinoma cells. Cancer Res. 51:1898-1903,