Dual Regulatory Mechanism of Itga6 on the Invasion and Radioresistance of Areca Nut Induced Head-Neck Cancer Cells

Head-neck cancer (HNC) is one of the most frequent malignant disease in Taiwan. it has tremendous impact on family and society. To systemically investigate the molecular carcinogenesis of HNC, our laboratory has previously established several HNC cell sublines with the characteristics of highly invasion, radioresistance, and chronic exposure to area nut extract. We have applied microarray analyses to evaluate transcriptomic profiles associated with these malignant phenotypes. To determine most prominent molecules significantly contribute to HNC, we have crossly examined the overlapped molecules among these microarray datasets. Numerous molecules have been filtered out, including ITGA6, indicating this molecule may play a crucial role in native HNC. ITGA6 (integrin-6) encodes a member of the integrin subunit, functioning in tissue architecture, member receptor, and participating in cell motility. Although integrin has been found participating in malignancy, reports of ITGA6 in HNC are very few, not related to areca nut. Apparently, ITGA6 is a novel molecule in the field of areca nut associated oncology. In this study, we propose to investigate how ITGA6 may be induced by areca nut and lead to HNC. The results of this study shall provide knowledge foundation for future application of ITGA6 in HNC, as in risk assessment, prognosis, or targeting therapeutics. The study aims are described below. Aim 1. Clinical assessment of ITGA6 in the progression and/or prognosis in HNC. Aim 1. Functional investigation of ITGA6 associated with cell invasion in HNC cells. Aim 2. Functional investigation of ITGA6 associated with radioresistance in HNC cells. Aim 3. Molecular investigation of ITGA6 downstream regulatory pathways in HNC cells. Aim 4. Mechanistic investigation of ITGA6 in response to areca nut exposure in HNC cells. Aim 6. Translational investigation of ITGA6 as a therapeutic target for intervention of HNC.

Project ID:PC10901-1948
External Project ID:MOST108-2320-B182-029-MY3