Abstract 4850: Tumor mitochondria contribute to autophagic properties of the cancer cells

Abstract

Abstract Autophagy is a cellular housekeeping process that removes damaged or unwanted cellular components and recycles them to build new constituents. It is essential for tumor growth under adverse environment. Mitochondria play an important role in the formation of autophagosome and its subsequent docking and fusion with lysosome. In order to study the contribution of mitochondria to the regulation of homeostatic autophagy in cancer cells, we used a transmitochondrial cytoplasmic hybrid (cybrid) system to investigate the role of tumor-derived mitochondria in a defined nuclear background. Since LC3-II is the autophagosomal membrane-bound form of microtubule-associated protein 1 light chain 3 (LC3-I), increased LC3-II or increased LC3-II/LC3-I ratio is an indication of activation of autophagy. Cybrids containing mitochondria derived from a highly metastatic breast cancer cell line MDA-MB-231 (c231) exhibited lower LC-II levels but higher ratio of LC3-II/LC-I than other cybrids containing mitochondria derived from low or moderate metastatic breast cancer cell lines MDA-MB-436 and MDA-MB-468, as well as mammary epithelial cell MCF-10A (c10A). Increase of LC3 puncta on immunofluorescence stain and decrease of sequestosome 1 (p62/SQSTM1), a marker of autophagic flux, in c231 cells, compared to other cybrids, further indicated that mitochondria derived from high metastatic breast cancer cell line MDA-MB-231 could increase autophagy and accelerate autophagic flux. The accelerated autophagic flux in c231 cells can be blocked by the autophagy inhibitor bafilomycin-A1. In addition, the mitochondria in c231 cells were noted to promote mitochondrial permeability transition (MPT) and were surrounded by LC3 puncta. These results suggested that tumor mitochondria from highly metastatic breast cancer cell line, MDA-MB-231, can promote homeostatic autophagy of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4850.