Abstract:
: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.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Jorand R,Biswas S,Wakefield DL,Tobin SJ,Golfetto O,Hilton K,Ko M,Ramos JW,Small AR,Chu P,Singh G,Jovanovic-Talisman Tdoi
10.1091/mbc.E16-06-0427subject
Has Abstractpub_date
2016-11-07 00:00:00pages
3659-3672issue
22eissn
1059-1524issn
1939-4586pii
mbc.E16-06-0427journal_volume
27pub_type
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