Abstract 1545: Loss of glycogen debranching enzyme (AGL) promotes rapid growth of non-small cell lung cancer cells

Abstract

Abstract Glycogen Debranching Enzyme (AGL) is involved in glycogen breakdown. Compromise in glycogen breakdown due to loss of function mutations in the AGL gene lead to metabolic disease - Glycogen Storage Disease Type III. We have previously shown that loss of AGL results in rapid growth of bladder cancer cells using extensive in vitro and in vivo experiments. Here we test whether AGL regulate growth of non-small cell lung cancer (NSCLC) cells. We show that loss of AGL promotes rapid growth of NSCLC cells using anchorage independent growth assay. Loss of AGL also resulted in rapid xenograft growth of NSCLC cells when injected subcutaneously in immunocompromised mice. Whereas overexpression of AGL reduce the growth of these NSCLC cells. Further loss of glycogen phosphorylase the other enzyme involved in glycogen breakdown does not promote aggressive growth of these cancer cells. This observation is similar to our findings in bladder cancer which confirms that AGL regulates tumor growth independent of its role in glycogen metabolism. Thus using in vitro and in vivo experiments we show that AGL can regulate the growth of multiple tumor types such as bladder cancer and NSCLC. The exact mechanism on how AGL regulates NSCLC growth needs further investigation. Citation Format: David R. Meier, Benjamin Weinhaus, Darby Oldenburg, Sunny Guin. Loss of glycogen debranching enzyme (AGL) promotes rapid growth of non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1545. doi:10.1158/1538-7445.AM2017-1545