Autophagy in Cancer Cells vs. Cancer Tissues: Two Different Stories
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Autophagy has been considered strongly associated with cancer development and possibly playing important roles in cancer progression. Here we present a computational study of transcriptomic data of cancer tissues, totaling 6317 tissue samples of 11 cancer types along with tissues of inflammatory diseases and cell line based experiments for comparative purposes. Our study clearly revealed that some widely held beliefs and speculations regarding autophagy in cancer may not be well founded, knowing that many of the previous observations were made on cancer cells cultured in man-made environments rather than actual cancer tissues. Our major findings include: (i) the widely used assumption that cancer tissue cells are nutrient depleted is not supported by our tissue-based gene-expression data analysis; (ii) the 11 cancer types studied fall into 2 distinct groups: those with low macro-autophagy (LM) activities and those with high lysosome (HL) activities but induced by micro-autophagy and chaperon-mediated autophagy; (ii) co-reduction in autophagy and apoptosis are widely observed in cancer tissues; (iii) down-regulated autophagy strongly correlates with up-regulated cell-cycle progression genes across all cancer types, with one possible functional link detected that repressed autophagosome formation may reduce the degradation of cellular organelles that are essential to cytokinesis, hence contributing to cell cycle progression; (iv) significant correlation is observed between autophagy and immune activities; (v) the down-regulated macro-autophagy genes negatively correlate with the total mutation rates in cancer genomes in LM cancers; and (vi) conditional correlation analyses point to a very unexpected direction: cellular Fenton reactions may be the cause of the decreased macro-autophagy and its co-expression with apoptosis, increased cell proliferation, genomic mutation rate and even possibly immune response. The information derived here may shed new light on elucidation of fundamental relationships between cancer and autophagy as well as on how to take advantage of the derived relationship for improved treatment of cancer.
KeywordsCancer Tissue Idiopathic Pulmonary Fibrosis Fenton Reaction Autophagosome Formation Renal Clear Cell Carcinoma
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