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Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein–coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor ce...

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Autores principales: Jorand, Raphael, Biswas, Sunetra, Wakefield, Devin L., Tobin, Steven J., Golfetto, Ottavia, Hilton, Kelsey, Ko, Michelle, Ramos, Joe W., Small, Alexander R., Chu, Peiguo, Singh, Gagandeep, Jovanovic-Talisman, Tijana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221597/
https://www.ncbi.nlm.nih.gov/pubmed/27682590
http://dx.doi.org/10.1091/mbc.E16-06-0427
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author Jorand, Raphael
Biswas, Sunetra
Wakefield, Devin L.
Tobin, Steven J.
Golfetto, Ottavia
Hilton, Kelsey
Ko, Michelle
Ramos, Joe W.
Small, Alexander R.
Chu, Peiguo
Singh, Gagandeep
Jovanovic-Talisman, Tijana
author_facet Jorand, Raphael
Biswas, Sunetra
Wakefield, Devin L.
Tobin, Steven J.
Golfetto, Ottavia
Hilton, Kelsey
Ko, Michelle
Ramos, Joe W.
Small, Alexander R.
Chu, Peiguo
Singh, Gagandeep
Jovanovic-Talisman, Tijana
author_sort Jorand, Raphael
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein–coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, here we combine traditional biochemical approaches with superresolution microscopy methods. A novel interaction specific to PDAC is identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2). Although MOR and SSTR2 did not colocalize in healthy pancreatic cells or matching healthy patient tissues, the pair did significantly colocalize in pancreatic cancer cells, multicellular tumor spheroids, and cancerous patient tissues. Moreover, this association in pancreatic cancer cells correlated with functional cross-talk and increased metastatic potential of cells. Coactivation of MOR and SSTR2 in PDAC cells led to increased expression of mesenchymal markers and decreased expression of an epithelial marker. Together these results suggest that the MOR-SSTR2 heteromer may constitute a novel therapeutic target for PDAC.
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spelling pubmed-52215972017-01-22 Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer Jorand, Raphael Biswas, Sunetra Wakefield, Devin L. Tobin, Steven J. Golfetto, Ottavia Hilton, Kelsey Ko, Michelle Ramos, Joe W. Small, Alexander R. Chu, Peiguo Singh, Gagandeep Jovanovic-Talisman, Tijana Mol Biol Cell Articles Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein–coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, here we combine traditional biochemical approaches with superresolution microscopy methods. A novel interaction specific to PDAC is identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2). Although MOR and SSTR2 did not colocalize in healthy pancreatic cells or matching healthy patient tissues, the pair did significantly colocalize in pancreatic cancer cells, multicellular tumor spheroids, and cancerous patient tissues. Moreover, this association in pancreatic cancer cells correlated with functional cross-talk and increased metastatic potential of cells. Coactivation of MOR and SSTR2 in PDAC cells led to increased expression of mesenchymal markers and decreased expression of an epithelial marker. Together these results suggest that the MOR-SSTR2 heteromer may constitute a novel therapeutic target for PDAC. The American Society for Cell Biology 2016-11-07 /pmc/articles/PMC5221597/ /pubmed/27682590 http://dx.doi.org/10.1091/mbc.E16-06-0427 Text en © 2016 Jorand, Biswas, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Jorand, Raphael
Biswas, Sunetra
Wakefield, Devin L.
Tobin, Steven J.
Golfetto, Ottavia
Hilton, Kelsey
Ko, Michelle
Ramos, Joe W.
Small, Alexander R.
Chu, Peiguo
Singh, Gagandeep
Jovanovic-Talisman, Tijana
Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
title Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
title_full Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
title_fullStr Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
title_full_unstemmed Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
title_short Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
title_sort molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221597/
https://www.ncbi.nlm.nih.gov/pubmed/27682590
http://dx.doi.org/10.1091/mbc.E16-06-0427
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