Exploring the DSG3 Signaling Pathway in the Regulation of Cellular Invasion/Growth and the Role in the Carcinogenesis of Head Neck Cancer

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Head and neck cancer (HNC) is the sixth most frequent cancer in the world with an estimated over 500,000 new cases being diagnosed annually. In Taiwan, the incidence of head and neck cancer has become the 7th leading cancer, the 5th leading cancer in male, and is still increasing in the recent years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society. For treatment, although local control and survival rates are acceptable for early staged tumor, in advanced tumor, bulk tumor or lymph node metastasis, that is, the highly invasive characteristic of the tumor is the common cause of treatment failure. Therefore, this malignant disease cannot be controlled, unless the better understanding of the molecular pathology in cancer growth and invasion as well as the advances of therapeutic techniques can been developed. Through differential display technique, we have previously identified several head and neck cancer-associated genes, including DSG3, which is over-expressed in the cancer tissues. DSG3 is a member of desmoglein family, belonging to the cadherin family of Ca(+2)-dependent cell adhesion molecules. We therefore hypothesize that over-expression of DSG3 is involved in the invasiveness and aggressiveness of head neck cancer, and that DSG3 is a potential target for molecular therapy of head neck cancer. The main objectives of this proposal are to investigate and clarify the functional role of DSG3 in the head and neck cancer, and investigate the potential application of modulating this molecular in cancer treatment. The following specific aims will be accomplished to unveil such questions. Specific Aim #1: Study in cellular level. Examination of the cellular effects of DSG3 after alteration of the DSG3 expression in cells. (1) Construction of the RNA interference plasmid and transfection of the gene into head neck cancer cells. (2) Study the effects of DSG3-RNAi in cellular homeostatsis, including cell growth/viability, colony formation, cell cycle distribution, cell migration and invasion ability. Specific Aim #2: Study in biochemical level. Investigation of the DSG3 signal pathway in cancer cells. (1) Examining the possible alteration of the potential down-stream signal targets of DSG3 molecules: β-catenin and plakoglobin after modulation of DSG3 by RNAi. (2) Examining the possible alteration of plakoglobin target in Tcf/Lef promoter genes (Tcf/Lef. c-myc, cyclin D1) leading to cell proliferation by luciferase reporter and western blot analysis. Specific Aim #3: Study in animal level. (1) Examining the effects of tumor growth and survival after DSG3-RNAi delivery into subcutaneous (for growth evaluation) or intravenous (for invasion evaluation) injected xenograft tumor mice using subcutaneous (for growth evaluation) or intravenous (for invasion evaluation) injection technique. (2) Examining the DSG3 expression in the tumor sections by immunohistochemistry. (3) Examining the histological apoptotic status. Specific Aim #4: Study in clinical level. Evaluation of DSG3 protein levels in the normal and cancer tissues. (2) Correlation of DSG3 expression with the cliniclpathological features and treatment outcome.

Project IDs

Project ID:PC9706-0154
External Project ID:NSC95-2320-B182-024-MY3
StatusFinished
Effective start/end date01/08/0831/07/09

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.