Short Communication
Autophagy: From Liver to Pancreas Tumor Pathogenesis
Pietro Di Fazio1* and Thaddeus Till Hippokrates Wissniowski2
1Department of Visceral Thoracic and Vascular Surgery, Philipps University of Marburg, Germany
2Department of Gastroenterology, Philipps University of Marburg, Germany
*Corresponding author: Pietro Di Fazio, Department of Visceral Thoracic and Vascular Surgery, Philipps University of Marburg, Germany
Published: 31 Jan, 2017
Cite this article as: Di Fazio P, Wissniowski TTH.
Autophagy: From Liver to Pancreas Tumor Pathogenesis. Clin Oncol. 2017; 2: 1198.
Short Communication
Autophagy is a fine regulated mechanism of recycling. It has been firstly discovered in yeast.
This self-eating, digestive mechanism is characterized by promoting the formation of double
membrane vesicles by the interaction of several autophagic proteins at endoplasmic reticulum
site [1]. Autophagy occurs during prolonged starvation and nutrient deprivation conditions. This
protracted stress causes sub cellular organelles dysfunction, e.g. mitochondria; the autophagy
machinery can internalize the non-functional organelles and drive them to the final digestion into
the lysosome vesicles [2]. Mammalian cells can activate this process under stress also. Protracted autophagy, caused by low ATP level, can lead to a complete auto digestion and cell demise finally
[3,4]. Altered autophagy process caused by the loss of function of autophagic key factors is implied in development of several diseases including neurodegenerative disorders and cancer [5]. Our studies focused on clarifying the autophagic processes in hepatocellular carcinoma. In particular, it
was observed that autophagy can be activated in liver cancer cells by treatment with the deacetylase
inhibitor panobinostat. The treatment caused an accumulation of autophagic genes transcripts
and protein products Beclin1 and Map1LC3B. Furthermore, the formation and the maturation of
autophagosomal vesicles were observed and followed in their maturation process (Figure1). The
possibility to target autophagy as cell death molecular mechanism in liver cancer could offer new
options for the palliative treatment of this, up to now, untreatable solid cancer [6]. The molecular mechanisms of autophagy represent a key role not only in liver cancer but also in other pathologies
related to liver, pancreas and in general to all digestive tract. Notably, it would be interesting to
clarify the role exerted by autophagy in NAFLD/NASH (non alcoholic fatty liver disease/non
alcoholic steatohepatitis) [7,8] in order to amplify the knowledge of molecular mechanisms related to this disease and to improve the current therapy [9,10]. Protracted NASH develops frequently in hepatocellular carcinoma [11] and the role exerted by autophagy in this pathology of the liver could give new efforts in the prevention and treatment of liver cancer. Furthermore, it has been recently
shown that autophagy plays a key role in pancreatic cancer and in particular autophagic mechanisms
resulted activated in pancreatic stellate cells surrounding pancreatic adenocarcinoma [12]. Up to now, it is not known, the role exerted by autophagy in pancreatic neuroendocrine tumors and the role exerted by stellate cells surrounding such kind of tumor of the pancreas.
The possibility to target autophagy, e.g. with mTOR (mammalian target of Rapamycin)
inhibitors [13] and other analogues, could represent a new strategy for a future therapy and a better
prognosis for patients affected by this highly recurrent and aggressive cancer of the pancreas.
Figure 1
Figure 1
HepG2 (left panel) and Hep3B (right panel) hepatocellular cancer cell lines stably transfected with
Map1LC3B-GFP-RFP tag. Treatment with panobinostat caused the green-red fluorescent puncta formation and
the red visualization indicating the autophagosome maturation process. Magnification is 400X and scale bar
indicates 10 μm.
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