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 COHR: Center for Oral Health Research | Projects | COBRE for Oral Health - Projects - Gunhild Sommer, PhD

Gunhild Sommer, PhD
Role of La in protection against chemotherapy-induced apoptosis in oral SCCOverview
gunhild sommer

Overview

The RNA-binding protein La is overexpressed in oral SCC tissue and its overexpression correlates with resistance to cisplatin treatment in oropharyngeal SCC cells. This project aims to elucidate the underlying molecular mechanism how overexpressed La contributes to resistance against chemotherapy in oral SCC.

Abstract

The RNA-binding protein La is overexpressed in oral SCC tissue and its overexpression correlates with resistance to cisplatin treatment in oropharyngeal SCC cells. This project aims to elucidate the underlying molecular mechanism how overexpressed La contributes to resistance against chemotherapy in oral SCC.


Chemotherapeutic drugs as cisplatin, 5-fluorouracil (5-FU) and docetaxol are the most widely used and effective agents in the treatment of advanced head and neck squamous cell carcinoma (SCC). However, failure of tumors to respond to treatment or tumor recurrence limits the overall success of these therapeutic approaches. Our long-term goal is to identify novel targets for therapeutic intervention by dissecting the molecular mechanism of how the RNA-binding protein La contributes to chemotherapy resistance in oral cancer.

The RNA-binding protein La is known to regulate mRNA translation of a number of cellular proteins. Our preliminary data demonstrate, that the La protein is overexpressed in oral SCC tissue and that overexpression of La correlates with protection against cisplatin-induced apoptosis and increased XIAP expression in oropharyngeal SCC cells. XIAP (X-linked inhibitor of apoptosis) is a well-known inhibitor of programmed cell death (apoptosis). It is overexpressed in various types of cancer, including oral cancer, and contributes to resistance of tumor cells to treatment with cisplatin, 5-FU and docetaxol. Interestingly, it has been shown that La stimulates internal ribosomal entry site (IRES)-dependent translation of XIAP and thereby stimulates its expression. Based on our preliminary data, we hypothesize that overexpression of La in oral cancer cells stimulates IRES-dependent XIAP translation and contributes to chemotherapy resistance.

This project will focus on the underlying mechanism of La-dependent XIAP-mRNA translation contributing to chemotherapy resistance in oral SCC. This knowledge will foster our future research on identification of novel molecular decoys to specifically inhibit the interaction of the La protein and XIAP mRNAs to reduce XIAP expression and improve the survival rate and response to chemotherapy of patients with oral cavity cancer.

 

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