Role of RABL6A in pancreatic neuroendocrine tumor development and progression

Pancreatic neuroendocrine tumors (pNETs) are rare and part of the diverse family of neuroendocrine neoplasms (NENs). Somatostatin receptors (SSTRs), which are widely expressed in NENs, are G-protein coupled receptors that can be activated by somatostatins or its synthetic analogs. Therefore, SSTRs have been widely researched as a diagnostic marker and therapeutic target in pNETs. A large number of studies have demonstrated the clinical significance of SSTRs in pNETs. In this review, relevant literature has been appraised to summarize the most recent empirical evidence addressing the clinical significance of SSTRs in pNETs. Overall, these studies have shown that SSTRs have great value in the diagnosis, treatment, and prognostic prediction of pNETs; however, further research is still necessary.

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Role of Somatostatins in Gastroenteropancreatic Neuroendocrine Tumor Development and Therapy

Gastroenterology ◽

10.1053/j.gastro.2010.07.002 ◽

2010 ◽

Vol 139 (3) ◽

pp. 742-753.e1 ◽

Cited By ~ 107

Author(s):

Kjell E. Öberg ◽

Jean–Claude Reubi ◽

Dik J. Kwekkeboom ◽

Eric P. Krenning

Keyword(s):

Neuroendocrine Tumor ◽

Tumor Development ◽

Gastroenteropancreatic Neuroendocrine Tumor

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Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development

Oncogene ◽

10.1038/onc.2011.337 ◽

2011 ◽

Vol 31 (11) ◽

pp. 1459-1467 ◽

Cited By ~ 61

Author(s):

S M Pyonteck ◽

B B Gadea ◽

H-W Wang ◽

V Gocheva ◽

K E Hunter ◽

...

Keyword(s):

Growth Factor ◽

Neuroendocrine Tumor ◽

Tumor Development ◽

Pancreatic Neuroendocrine Tumor

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Role of palliative resection of the primary pancreatic neuroendocrine tumor in patients with unresectable metastatic liver disease: a systematic review and meta-analysis

OncoTargets and Therapy ◽

10.2147/ott.s158171 ◽

2018 ◽

Vol Volume 11 ◽

pp. 975-982 ◽

Cited By ~ 13

Author(s):

Bo Zhou ◽

Canyang Zhan ◽

Yuan Ding ◽

Sheng Yan ◽

Shusen Zheng

Keyword(s):

Systematic Review ◽

Liver Disease ◽

Neuroendocrine Tumor ◽

Meta Analysis ◽

Pancreatic Neuroendocrine Tumor ◽

Palliative Resection ◽

Metastatic Liver

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24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613332113 ◽

2016 ◽

Vol 113 (41) ◽

pp. E6219-E6227 ◽

Cited By ~ 16

Author(s):

Matias Soncini ◽

Gianfranca Corna ◽

Marta Moresco ◽

Nadia Coltella ◽

Umberto Restuccia ◽

...

Keyword(s):

Neuroendocrine Tumor ◽

Molecular Mechanisms ◽

Hypoxia Inducible Factor ◽

Tumor Development ◽

Pancreatic Neuroendocrine Tumor ◽

Tumor Diameter ◽

Angiogenic Switch ◽

Tumor Microenvironments ◽

Oxidized Products ◽

Protumoral Activities

Cells in the tumor microenvironment may be reprogrammed by tumor-derived metabolites. Cholesterol-oxidized products, namely oxysterols, have been shown to favor tumor growth directly by promoting tumor cell growth and indirectly by dampening antitumor immune responses. However, the cellular and molecular mechanisms governing oxysterol generation within tumor microenvironments remain elusive. We recently showed that tumor-derived oxysterols recruit neutrophils endowed with protumoral activities, such as neoangiogenesis. Here, we show that hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol (24S-HC) in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α–24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1+ islets. Pharmacologic blockade or genetic inactivation of oxysterols controls pNET tumorigenesis by dampening the 24S-HC–neutrophil axis. Finally, we show that in some human pNET samples Cyp46a1 transcripts are overexpressed, which correlate with the HIF-1α target VEGF and with tumor diameter. This study reveals a layer in the angiogenic switch of pNETs and identifies a therapeutic target for pNET patients.

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