Abstract 1493: LonP1 is required for tumor maintenance and growth

Proper mitochondrial function is critical for energy production and the cycling of metabolites required for tumor establishment and growth. LonP1 is an ATP-dependent serine protease that is critical for maintaining mitochondrial protein homeostasis by degrading misfolded and damaged proteins in the mitochondrial matrix. Knockdown of LonP1 has been shown to reduce tumorogenesis and is consistent with the model that requires properly functioning mitochondria for tumor establishment. It is unclear what the role of LonP1 is in tumor maintenance and growth from an established tumor, therefore the LonP1 gene was mutated and complemented by a doxycycline-inducible copy of LonP1. These complementation clones have the ability to establish tumors in vivo in the presence of doxycycline, however upon doxycycline withdrawal the tumors regress and show evidence of apoptosis. These xenograft lines permit unique insight into not only potential LonP1 substrates but also the direct and indirect effects from loss of mitochondrial matrix protein homeostasis. Comparison and contrast of these complemented cell lines in vitro and in vivo by expression and proteomic analysis will be discussed. Citation Format: Benjamin S. Amidon, Dongyun Wu, John Bradley, Jingya Ma, Christopher Tsu, Elizabeth Carideo-Cunniff, Vihren Kolev, James Garnsey, Pooja Shah, Erik Koenig, Hua Liao, Courtney Cullis. LonP1 is required for tumor maintenance and growth [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 1493. doi:10.1158/1538-7445.AM2017-1493