Role of Nuclear Egfr in Dna Repair and Chemoresistance

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

Project Details


Epidermal Growth factor receptor (EGFR) is the prototype member of receptor tyrosine kinase (RTK). Upon ligand binding, the receptor dimer formation activates protein tyrosine kinase then initiates several cellular signaling cascades to regulate cell proliferation, differentiation and survival. In addition to the role of initiator of traditional signal pathway, several reports have shown that EGFR is detected in the nucleus in several types of normal and cancer cells. EGFR overexpression or activation has been implicated in the pathogenesis and resistance to radiotherapy or chemotherapy of several human tumors including the lung, breast, ovary, head and neck. Nuclear EGFR has also been found in breast carcinoma and oropharyngeal squamous cell cancer, and serves as a poor prognostic marker. Recent studies show that in addition to EGF, ionizing radiation (IR) and cisplatin are able to induce EGFR nuclear localization. However, the molecular mechanisms of EGFR nuclear translocation induced by DNA damage agents and how nuclear EGFR contributes to DNA repair and chemoresistance remain unclear. Thus, three specific aims are proposed in this research project as follows: (1) to examine the mechanisms of DNA damage-induced EGFR nuclear translocation; (2) to identify and characterize the nuclear EGFR interacting proteins under DNA damage to explore the role of nuclear EGFR in DNA repair; and (3) to identify the novel nuclear EGFR target genes under DNA damage using systemic and non-biased approach. Success of this proposal will greatly extent our knowledge of biological functions of nuclear EGFR, and will likely lead to discovery of new prognostic markers and development of new approaches for anti-cancer therapy.

Project IDs

Project ID:PA10101-1136
External Project ID:NSC99-2311-B182-005-MY3
Effective start/end date01/08/1231/07/13


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.