The role of metabolic adaptation to nutrient stress in pancreatic cancer

Derle, Abhishek; Santis, Maria Chiara De; Gozzelino, Luca; Ratto, Edoardo; Martini, Miriam

The role of metabolic adaptation to nutrient stress in pancreatic cancer

Authors:

Abhishek Derle^1,#, Maria Chiara De Santis^1,#, Luca Gozzelino^1,#, Edoardo Ratto^1,# and Miriam Martini¹

Affiliations:

¹ Department of Molecular Biotechnology and Health Science, Molecular Biotechnology Center, University of Torino, Torino, Italy.

^# Contributed equally to this manuscript.

Keywords:

pancreatic cancer, nutrient stress, metabolic rewiring, autophagy, macropinocytosis.

Abbreviations:

α-KG – α-ketoglutarate,

GOT1 – Glutamic-oxaloacetic transaminase,

mTOR – mammalian target of rapamycin,

PDAC – pancreatic ductal adenocarcinoma,

PPP – pentose phosphate pathway,

TCA – tricarboxylic acid.

Corresponding Author(s):

Miriam Martini, Department of Molecular Biotechnology and Health Science, Molecular Biotechnology Center, via Nizza 52, 10126, Torino, Italy; Phone: +39-11-6706425 miriam.martini@unito.it

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Abhishek Derle, Maria Chiara De Santis, Luca Gozzelino, Edoardo Ratto and Miriam Martini (2018). The role of metabolic adaptation to nutrient stress in pancreatic cancer. Cell Stress 2(12): 332-339. doi: 10.15698/cst2018.12.166

© 2018 Derle et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Pancreatic cancer is the fourth most common cause of cancer-related mortality, with a dismal prognosis that has changed little over the past few decades. Despite extensive efforts in understanding the oncogenetics of this pathology, pancreatic cancer remained largely elusive. One of the main characteristics of pancreatic cancer is the reduced level of oxygen and nutrient perfusion, caused by the new matrix formation, through the activation of stromal cells (desmoplasia). This stromal reaction leads to metabolic adaptations in surviving tumor cells in order to cope with these challenging conditions. The oncogenic signaling driven by KRAS mutation is necessary to fuel pancreatic tumors by activating key metabolic processes, including enhanced glycolysis and glutamine consumption. Here we review our current understanding of the pancreatic cancer metabolism as well as discuss recent work pointing to the importance of various metabolic strategies as well as autophagy and macropinocytosis as critical nutrient supply pathways. The elucidation of these metabolic networks may highlight new opportunities to further develop novel therapeutic strategies.