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Targeting cancer cell metabolism in pancreatic adenocarcinoma.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided.

SUBMITTER: Cohen R

PROVIDER: S-EPMC4627277 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Targeting cancer cell metabolism in pancreatic adenocarcinoma.

Cohen Romain R Neuzillet Cindy C Tijeras-Raballand Annemilaï A Faivre Sandrine S de Gramont Armand A Raymond Eric E

Oncotarget 20150701 19

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic repro ...[more]

PMID: 26164081

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Project description:Hox transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) that serves a key role in the pathogenesis of various types of cancer, including pancreatic adenocarcinoma. However, the diagnostic and prognostic values of HOTAIR in pancreatic adenocarcinoma, as well as its involvement in cancer cell energy metabolism, remain unclear. In the present study, tumor tissues and adjacent healthy tissues were collected from patients with pancreatic adenocarcinoma, and blood samples were collected from patients and healthy controls. Expression levels of HOTAIR and hexokinase-2 (HK2) were detected by reverse transcription-quantitative polymerase chain reaction. All patients were followed up for 5 years, and the diagnostic and prognostic values of serum HOTAIR levels were investigated by receiver operating characteristic curve and survival analyses, respectively. Pancreatic adenocarcinoma cell lines overexpressing HOTAIR and HK2 were established, and the effects on cell proliferation, lactate production, glucose uptake and ATP production were detected by Cell Counting Kit-8, lactate, glucose uptake and ATP assays, respectively. The protein expression was detected by western blot analysis. The results revealed that HOTAIR and HK2 expression levels were increased in tumor tissues compared with adjacent healthy tissues. The serum levels of HOTAIR and HK2 were higher in patients with pancreatic cancer compared with healthy controls. The serum levels of these two factors may be used to accurately predict pancreatic adenocarcinoma and its prognosis. HOTAIR and HK2 overexpression led to the promotion of tumor cell proliferation. HOTAIR overexpression increased lactate production, glucose uptake and ATP production. Furthermore, it promoted HK2 expression, however HK2 overexpression displayed no significant effects on HOTAIR expression levels. Therefore, it was concluded that the lncRNA HOTAIR may promote cancer cell energy metabolism in pancreatic adenocarcinoma by upregulating HK2.

Dataset Information

Targeting cancer cell metabolism in pancreatic adenocarcinoma.

Publications

Targeting cancer cell metabolism in pancreatic adenocarcinoma.

Similar Datasets

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