Pancreatic adenocarcinoma, chronic pancreatitis, and MODY-8 diabetes: is bile salt-dependent lipase (or carboxyl ester lipase) at the crossroads of pancreatic pathologies?

Dominique Lombardo _, Françoise Silvy, Isabelle Crenon, Emmanuelle Martinez, Aurélie Collignon, Evelyne Beraud and Eric Mas

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Oncotarget. 2018; 9:12513-12533. https://doi.org/10.18632/oncotarget.23619

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Dominique Lombardo1, Françoise Silvy1, Isabelle Crenon1, Emmanuelle Martinez1, Aurélie Collignon1, Evelyne Beraud1 and Eric Mas1

1Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie Biologique et Oncopharmacologie, Marseille, France

Correspondence to:

Dominique Lombardo, email: [email protected]

Keywords: pancreatic adenocarcinoma; chronic pancreatitis; diabetes; bile salt-dependent lipase; carboxyl ester lipase

Received: May 07, 2017     Accepted: November 06, 2017     Published: December 22, 2017


Pancreatic adenocarcinomas and diabetes mellitus are responsible for the deaths of around two million people each year worldwide. Patients with chronic pancreatitis do not die directly of this disease, except where the pathology is hereditary. Much current literature supports the involvement of bile salt-dependent lipase (BSDL), also known as carboxyl ester lipase (CEL), in the pathophysiology of these pancreatic diseases. The purpose of this review is to shed light on connections between chronic pancreatitis, diabetes, and pancreatic adenocarcinomas by gaining an insight into BSDL and its variants. This enzyme is normally secreted by the exocrine pancreas, and is diverted within the intestinal lumen to participate in the hydrolysis of dietary lipids. However, BSDL is also expressed by other cells and tissues, where it participates in lipid homeostasis. Variants of BSDL resulting from germline and/or somatic mutations (nucleotide insertion/deletion or nonallelic homologous recombination) are expressed in the pancreas of patients with pancreatic pathologies such as chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We discuss the possible link between the expression of BSDL variants and these dramatic pancreatic pathologies, putting forward the suggestion that BSDL and its variants are implicated in the cell lipid metabolism/reprogramming that leads to the dyslipidemia observed in chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We also propose potential strategies for translation to therapeutic applications.

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