Telomere Maintenance and the cGAS-STING Pathway in Cancer

Abstract

Cancer cells exhibit the unique characteristics of high proliferation and aberrant DNA damage response, which prevents cancer therapy from effectively eliminating them. The machinery required for telomere maintenance, such as telomerase and the alternative lengthening of telomeres (ALT), enables cancer cells to proliferate indefinitely. In addition, the molecules in this system are involved in noncanonical pro-tumorigenic functions. Of these, the function of the cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contains telomere-related molecules, is a well-known contributor to the tumor microenvironment (TME). This review summarizes the current knowledge of the role of telomerase and ALT in cancer regulation, with emphasis on their noncanonical roles beyond telomere maintenance. The components of the cGAS-STING pathway are summarized with respect to intercell communication in the TME. Elucidating the underlying functional connection between telomere-related molecules and TME regulation is important for the development of cancer therapeutics that target cancer-specific pathways in different contexts. Finally, strategies for designing new cancer therapies that target cancer cells and the TME are discussed.

Keywords

• DNA damage
• telomere
• cGAS-STING
• cancer
• ALT
• cellular senescence