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The role of DDX11 in telomere maintenance in cancer cells
Thesis

The role of DDX11 in telomere maintenance in cancer cells

Manasvi Sheta
Master of Science (M.S.), Drexel University
Apr 2025
DOI:
https://doi.org/10.17918/00010923
pdf
Manasvi_Sheta_20251.36 MB
PDF Embargoed Access, Embargo ends: 30 Jun 2027

Abstract

Cancer Biology
Telomeres maintain the structural integrity of chromosomal ends. They are a promising target of cancer therapeutics because cancer cells rely on telomeres for their proliferation. Telomeres are enriched with G-quadruplexes (G4s), four-stranded DNA structures stabilized by the formation of bonds between guanine nucleotides. G4 ligands have been developed to target these structures to disrupt telomere integrity and induce DNA damage, leading to cellular senescence. The DDX1 helicase, which is proposed to facilitate DNA replication of G4-containing sequences, interacts with Timeless, a protein which prevents telomere shortening. Studies have reported that DDX11 is overexpressed in various cancer cells including esophageal squamous cell carcinoma (ESCC), suggesting that DDX11 may play a role in the progression of cancers. This study aims to understand the role of DDX11 in TE-11, an esophageal squamous cell carcinoma cell line. We found that RNAi-mediated DDX11 downregulation results in the inhibition of ESCC cell proliferation. We also found that DDX11 promotes telomere maintenance. We will discuss the role of DDX11 in controlling cellular senescence and telomere maintenance. Our results are expected to contribute to the development of anticancer therapeutics.

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