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 investigation.
To recapitulate the molecular events underlying tumor metastasis and to uncover a series of therapeutic targets for esophageal squamous cell carcinoma, we employed Affymetrix microarray profiling to delineate the molecular portrait of esophageal carcinoma specimens. Using these microarray datasets, transformation of the gene expression signatures into protein network, we identification a set of genes which could serve as the minimal discriminators for esophageal carcinoma. Within these genes, TGFBI was chose for further study. Currently, we are analyzing the association and the functions of this gene in esophageal carcinoma metastasis.
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 the target genes regulated by IRF6 in palate epithelial cells during palate formation also will be identified. 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.
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: 10.1007/s10495-010-0555-z, 2010.
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, 2002.
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, 1991.