ATG5 and ATG7 Expression Levels Are Reduced in Cutaneous Melanoma and Regulated by NRF1.

Autophagy is a highly conserved cellular process in which intracellular proteins and organelles are sequestered and degraded after the fusion of double-membrane vesicles known as autophagosomes with lysosomes. The process of autophagy is dependent on autophagy-related (ATG) proteins. The role of autophagy in cancer is very complex and still elusive.

Machine learning with autophagy-related proteins for discriminating renal cell carcinoma subtypes.

Machine learning techniques have been previously applied for classification of tumors based largely on morphological features of tumor cells recognized in H&E images. Here, we tested the possibility of using numeric data acquired from software-based quantification of certain marker proteins, i.e.

ATG12 deficiency leads to tumor cell oncosis owing to diminished mitochondrial biogenesis and reduced cellular bioenergetics.

In contrast to the "Warburg effect" or aerobic glycolysis earlier generalized as a phenomenon in cancer cells, more and more recent evidence indicates that functional mitochondria are pivotal for ensuring the energy supply of cancer cells. Here, we report that cancer cells with reduced autophagy-related protein 12 (ATG12) expression undergo an oncotic cell death, a phenotype distinct from that seen in ATG5-deficient cells described before. In addition, using untargeted metabolomics with ATG12-deficient cancer cells, we observed a global reduction in cellular bioenergetic pathways, such as β-oxidation (FAO), glycolysis, and tricarboxylic acid cycle activity, as well as a decrease in mitochondrial respiration as monitored with Seahorse experiments.

Downregulation of Autophagy-Related Proteins 1, 5, and 16 in Testicular Germ Cell Tumors Parallels Lowered LC3B and Elevated p62 Levels, Suggesting Reduced Basal Autophagy.

Autophagy is a cellular "self-digestion" process known to be essential for various physiological and pathological pathways, including cancer, where its role appears to be context-dependent. In this work, we aimed to investigate the level of autophagy by evaluating the expression of key autophagy-related proteins (ATGs) in testicular germ cell tumors (TGCT) for which autophagy has been rarely investigated. We decided to use an immunohistochemical (IHC) staining approach employing a tissue microarray (TMA).

Biochemical re-programming of human dermal stem cells to neurons by increasing mitochondrial membrane potential.

Stem cells are generally believed to contain a small number of mitochondria, thus accounting for their glycolytic phenotype. We demonstrate here, however, that despite an indispensable glucose dependency, human dermal stem cells (hDSCs) contain very numerous mitochondria. Interestingly, these stem cells segregate into two distinct subpopulations.

BOK promotes chemical-induced hepatocarcinogenesis in mice.

BCL-2-related ovarian killer (BOK) is a conserved and widely expressed BCL-2 family member with sequence homology to pro-apoptotic BAX and BAK, but with poorly understood pathophysiological function. Since several members of the BCL-2 family are critically involved in the regulation of hepatocellular apoptosis and carcinogenesis we aimed to establish whether loss of BOK affects diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Short-term exposure to DEN lead to upregulation of BOK mRNA and protein in the liver.

Neutrophil Necroptosis Is Triggered by Ligation of Adhesion Molecules following GM-CSF Priming.

Apoptosis is the most common form of neutrophil death under both physiological and inflammatory conditions. However, forms of nonapoptotic neutrophil death have also been observed. In the current study, we report that human neutrophils undergo necroptosis after exposure to GM-CSF followed by the ligation of adhesion receptors such as CD44, CD11b, CD18, or CD15.

p73 regulates basal and starvation-induced liver metabolism in vivo.

As a member of the p53 gene family, p73 regulates cell cycle arrest, apoptosis, neurogenesis, immunity and inflammation. Recently, p73 has been shown to transcriptionally regulate selective metabolic enzymes, such as cytochrome c oxidase subunit IV isoform 1, glucose 6-phosphate dehydrogenase and glutaminase-2, resulting in significant effects on metabolism, including hepatocellular lipid metabolism, glutathione homeostasis and the pentose phosphate pathway. In order to further investigate the metabolic effect of p73, here, we compared the global metabolic profile of livers from p73 knockout and wild-type mice under both control and starvation conditions.

Protective role of autophagy and autophagy-related protein 5 in early tumorigenesis.

Autophagy, a fundamental cellular catabolic process, is involved in the development of numerous diseases including cancer. Autophagy seems to have an ambivalent impact on tumor development. While increasing evidence indicates a cytoprotective role for autophagy that can contribute to resistance against chemotherapy and even against the adverse, hypoxic environment of established tumors, relatively few publications focus on the role of autophagy in early tumorigenesis.

Autophagy suppresses melanoma tumorigenesis by inducing senescence.

Whether and how autophagy is involved in tumorigenesis is poorly understood. We approached this question by investigating a relatively large cohort of patients with mostly early primary melanoma for their expression of 2 markers for autophagy, the protein ATG5 (autophagy-related 5) and MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3B). Surprisingly, we discovered that both ATG5 and LC3 levels are decreased in patients with melanomas as compared with those with benign nevi.

Down-regulation of autophagy-related protein 5 (ATG5) contributes to the pathogenesis of early-stage cutaneous melanoma.

The role of autophagy in cancer is controversial: Both tumor-suppressing and tumor-promoting functions have been reported. We show that a key regulator of autophagy, autophagy-related protein 5 (ATG5), is often down-regulated in primary melanomas compared to benign nevi, leading to a reduction of basal autophagy as evidenced by a reduced expression of LC3. A follow-up of 158 primary melanoma patients showed that patients with low levels of ATG5 in their tumors had a reduced progression-free survival.

Targeting autophagy as a potential therapeutic approach for melanoma therapy.

Melanoma, occurring as a rapidly progressive skin cancer, is resistant to current chemo- and radiotherapy, especially after metastases to distant organs has taken place. Most chemotherapeutic drugs exert their cytotoxic effect by inducing apoptosis, which, however, is often deficient in cancer cells. Thus, it is appropriate to attempt the targeting of alternative pathways, which regulate cellular viability.