Autophagy and tumorigenesis

Department of Pathology, Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
FEBS letters (Impact Factor: 3.34). 04/2010; 584(7):1427-35. DOI: 10.1016/j.febslet.2009.12.034
Source: PubMed

ABSTRACT Autophagy, or cellular self-digestion, is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Nonetheless, genetic evidence supports that autophagy functions as a tumor suppressor mechanism. Hence, the precise role of autophagy during cancer progression and treatment is both tissue and context dependent. Here, we discuss our current understanding of the biological functions of autophagy during cancer development, overview how autophagy is regulated by cancer-associated signaling pathways, and review how autophagy inhibition is being exploited to improve clinical outcomes.

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    • "More importantly, the best hope for cancer therapeutics may lie in discovering candidate agents targeting core survival/death pathways and even the autophagy-related cancer networks, rather than their individual gene or protein (Turcotte and Giaccia, 2010; Chen et al., 2010). Within this context, further elucidating the complicated survival or death mechanisms and targeting core autophagic pathways would be a promising avenue for discovering potential new anti-neoplastic drug targets from bench to clinic. "
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    • "Gastroenterology Research and Practice tumorigenesis [7] [8] [9] [10]. In this study, suppression subtractive hybridization (SSH) was used to identify genes that are overexpressed in esophageal cancer cells. "
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    ABSTRACT: To find genes involved in tumorigenesis and the development of esophageal cancer, the suppression subtractive hybridization (SSH) method was used to identify genes that are overexpressed in esophageal cancer tissues compared to normal esophageal tissues. In our SSH library, the forkhead box O3 (FOXO3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and myeloid differentiation primary response 88 (MYD88) genes were the most highly upregulated genes, and they were selected for further studies because of their potential role in the induction of autophagy. Upregulation of these genes was also observed in clinical samples using qRT-PCR. In addition, coexpression analysis of the autophagy-related genes Beclin1, ATG12, Gabarapl, PIK3C3, and LC3 demonstrated a significant correlation between the differentially overexpressed genes and autophagy. Autophagy is an important mechanism in tumorigenesis and the development of chemoresistance in cancer cells. The upregulation of FOXO3, GAPDH, and MYD88 variants in esophageal cancer suggests a role for autophagy and provides new insight into the biology of esophageal cancer. We propose that FOXO3, GAPDH, and MYD88 are novel targets for combating autophagy in esophageal cancer.
    Gastroenterology Research and Practice 01/2014; 2014:185035. DOI:10.1155/2014/185035 · 1.75 Impact Factor
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    • "The role of autophagy as a survival mechanism in response to these diverse stressors has been well established . Moreover , it has become increasingly clear that a basal level of autophagy serves as housekeeping functions vital for maintaining cellular homeostasis ; especially , the failure to clear protein aggregates or damaged organelles by autophagy has been implicated in multiple pathological conditions , including cancer ( Chen and Debnath , 2010 ) . Terpinen - 4 - ol is a terpene that usually found as a main component in essential oil from plants , such as rhizomes of Cassumunar ginger ; Plai in Thai ; ( Zingiber montanum ( Koenig ) Link ex Dietr . "
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    ABSTRACT: Background: Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Materials and Methods: The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.
    Asian Pacific journal of cancer prevention: APJCP 12/2013; 14(12):7537-42. DOI:10.7314/APJCP.2013.14.12.7537 · 2.51 Impact Factor
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