Molecular mediators of peritoneal metastasis in pancreatic cancer

Abstract

Pancreatic cancer is the third leading cause of cancer death in the USA, and pancreatic ductal adenocarcinoma (PDA) constitutes 85% of pancreatic cancer diagnoses. PDA frequently metastasizes to the peritoneum, but effective treatment of peritoneal metastasis remains a clinical challenge. Despite this unmet need, understanding of the biological mechanisms that contribute to development and progression of PDA peritoneal metastasis is sparse. By contrast, a vast number of studies have investigated mechanisms of peritoneal metastasis in ovarian and gastric cancers. Here, we contrast similarities and differences between peritoneal metastasis in PDA as compared with those in gastric and ovarian cancer by outlining molecular mediators involved in each step of the peritoneal metastasis cascade. This review aims to provide mechanistic insights that could be translated into effective targeted therapies for patients with peritoneal metastasis from PDA.

MicroRNA-505, Suppressed by Oncogenic Long Non-coding RNA LINC01448, Acts as a Novel Suppressor of Glycolysis and Tumor Progression Through Inhibiting HK2 Expression in Pancreatic Cancer

“…Tumor cells are known for their increased glucose uptake rates even in the presence of abundant oxygen, defined as the Warburg effect (Avula et al, 2020 ). HK2 catalyzes the first committed step of glucose metabolism and is critically important for aerobic glycolysis in multiple cancer types (Stolfi et al, 2013 ).…”

“…The 5-year overall survival rate of PC has remained low at 6% (Garrido-Laguna and Hidalgo, 2015 ). PC is usually detected at advanced tumor stages when the disease has metastasized (Avula et al, 2020 ). Cancer metastasis is the leading cause of PC-related mortality (Sergeant et al, 2009 ; Avula et al, 2020 ).…”

“…PC is usually detected at advanced tumor stages when the disease has metastasized (Avula et al, 2020 ). Cancer metastasis is the leading cause of PC-related mortality (Sergeant et al, 2009 ; Avula et al, 2020 ). Thus, interventions to development and metastasis are critical for a favorable outcome.…”

“…Thus, interventions to development and metastasis are critical for a favorable outcome. A growing body of evidence suggested that cancer stem cells constitute a distinct subpopulation in the tumor and play pivotal roles in tumor initiation and progression of PC (Sergeant et al, 2009 ; Avula et al, 2020 ). Moreover, most tumor cells highly rely on aerobic glycolysis to produce energy rather than mitochondrial oxidative phosphorylation even in the presence of oxygen, this is known as the “Warburg effect” (Avula et al, 2020 ).…”

“…A growing body of evidence suggested that cancer stem cells constitute a distinct subpopulation in the tumor and play pivotal roles in tumor initiation and progression of PC (Sergeant et al, 2009 ; Avula et al, 2020 ). Moreover, most tumor cells highly rely on aerobic glycolysis to produce energy rather than mitochondrial oxidative phosphorylation even in the presence of oxygen, this is known as the “Warburg effect” (Avula et al, 2020 ). Hexokinase 2 (HK2) is a cancer-associated isoenzyme that catalyzes the first rate-limiting step of glucose metabolism, and depletion of HK2 in PC cell lines decreased lactate production, invasion, and metastasis (Anderson et al, 2016 ).…”