TY - JOUR
T1 - An integrative view on glucagon function and putative role in the progression of pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC)
AU - Ferreira, Bárbara
AU - Heredia, Adrián
AU - Serpa, Jacinta
N1 - Funding Information:
The institutions are funded by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health ( UIDB/04462/2020 and UIDP/04462/2020 ) and the Associated Laboratory LS4FUTURE ( LA/P/0087/2020 ).
Funding Information:
Lipids metabolism is relevant to sustain pNETs and HCC. Little is known on lipids metabolism in pNETs cancer models, but in pNETs patients, a poor prognosis association was observed with increased levels of expression of acetyl-Co carboxylase 1 (ACC1) and FA synthase (FASN), moreover this study supported that systemic and tumour increased lipid bioavailability are associated with decreased progression-free survival (PFS) of advanced pNETs patients treated with everolimus, a mTOR inhibitor (Vernieri et al., 2019a). The inhibition of mTOR is an important therapeutical approach since abnormal PI3K-Akt/PKB-mTOR pathway signalling has been implicated in the pathogenesis of pNETs (Goldstein and Meyer, 2011). Interestingly, everomilus present as side effects hyperglycaemia, hyperglyceridaemia and hypercholesterolaemia (Vernieri et al., 2019b), indicating that PI3K pathway interferes with metabolism and is a core controller of pNETs’ metabolic remodelling, in which glucagon may be a key activator. In HCC, the upregulation of FAs anabolism and catabolism, as well as the increased uptake is described as crucial in tumorigenesis and disease progression, as reviewed (Sangineto et al., 2020b). The FA metabolic usage is dependent on the TOME and the genetic profile of tumours, varying according to the clinical context of HCC. Upon oxygen and nutrients scarcity, β-catenin-activated HCC cells increase the uptake of FA from the TOME together with the β-oxidation rate (Iwamoto et al., 2018). Although β-oxidation suppression favoured HCC development in obesity and non-alcoholic steatohepatitis (NASH) contexts (Sangineto et al., 2020c). FA de novo synthesis also has a role in tumoral progression, since ACC1 enzyme has been associated with HCC cell survival under glucose scarcity (Wang et al., 2016c). Furthermore, the fundamental role of FASN in HCC has been demonstrated by genetic silencing and enzyme inhibition, in studies dedicated to HCC in vitro and in vivo models (Calvisi et al., 2011; HAO et al., 2014; Li et al., 2016).The institutions are funded by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020) and the Associated Laboratory LS4FUTURE (LA/P/0087/2020).
Publisher Copyright:
© 2023 The Authors
PY - 2023/9/7
Y1 - 2023/9/7
N2 - Cancer metabolism research area evolved greatly, however, is still unknown the impact of systemic metabolism control and diet on cancer. It makes sense that systemic regulators of metabolism can act directly on cancer cells and activate signalling, prompting metabolic remodelling needed to sustain cancer cell survival, tumour growth and disease progression. In the present review, we describe the main glucagon functions in the control of glycaemia and of metabolic pathways overall. Furthermore, an integrative view on how glucagon and related signalling pathways can contribute for pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC) progression, since pancreas and liver are the major organs exposed to higher levels of glucagon, pancreas as a producer and liver as a scavenger. The main objective is to bring to discussion some glucagon-dependent mechanisms by presenting an integrative view on microenvironmental and systemic aspects in pNETs and HCC biology.
AB - Cancer metabolism research area evolved greatly, however, is still unknown the impact of systemic metabolism control and diet on cancer. It makes sense that systemic regulators of metabolism can act directly on cancer cells and activate signalling, prompting metabolic remodelling needed to sustain cancer cell survival, tumour growth and disease progression. In the present review, we describe the main glucagon functions in the control of glycaemia and of metabolic pathways overall. Furthermore, an integrative view on how glucagon and related signalling pathways can contribute for pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC) progression, since pancreas and liver are the major organs exposed to higher levels of glucagon, pancreas as a producer and liver as a scavenger. The main objective is to bring to discussion some glucagon-dependent mechanisms by presenting an integrative view on microenvironmental and systemic aspects in pNETs and HCC biology.
KW - GCGR
KW - Glucagon
KW - HCC
KW - Metabolic remodelling
KW - pNETs
KW - Signalling pathways
UR - http://www.scopus.com/inward/record.url?scp=85171750367&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2023.112063
DO - 10.1016/j.mce.2023.112063
M3 - Review article
C2 - 37678603
AN - SCOPUS:85171750367
SN - 0303-7207
VL - 578
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 112063
ER -
