Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer.
Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer.
复制标题
胰腺癌中MU阿片受体和生长抑素受体2的分子特征。
DOI：
10.1091/mbc.e16-06-0427
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发表时间：
2016-11-07
影响因子：
3.3
通讯作者：
Jovanovic-Talisman T
中科院分区：
文献类型：
--
作者：
Jorand R;Biswas S;Wakefield DL;Tobin SJ;Golfetto O;Hilton K;Ko M;Ramos JW;Small AR;Chu P;Singh G;Jovanovic-Talisman T
Superresolution microscopy and biochemical approaches identify a novel interaction between MOR and SSTR2 specific to pancreatic ductal adenocarcinoma. Coactivation of the two receptors leads to a distinct signaling pathway, consistent with β-arrestin2 signaling and the increased metastatic potential of pancreatic cancer cells. 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.
