title: β2-adrenergic receptor signaling promotes pancreatic ductal adenocarcinoma (PDAC) progression through facilitating PCBP2-dependent c-myc expression.
abstract: The β2-adrenergic receptor (β2-AR) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) progression. In this report, we identified poly(rC)-binding protein 2 (PCBP2) as a novel binding partner for β2-AR using immunoprecipitation-mass spectrometry (IP-MS) approach. The association between β2-AR and PCBP2 was verified using reciprocal immunoprecipitation. Importantly, we found significant interaction and co-localization of the two proteins in the presence of β2-AR agonist in Panc-1 and Bxpc3 PDAC cells. β2-AR-induced recruitment of PCBP2 led to augmented protein level of c-myc in PDAC cells, likely as a result of enhanced internal ribosome entry segment (IRES)-mediated translation of c-myc. The activation of β2-AR accelerated cell proliferation and colony formation, while knockdown of PCBP2 or c-myc restrained the effect. Furthermore, overexpression of PCBP2 was observed in human PDAC cell lines and tissue specimens compared to the normal pancreatic ductal epithelial cells and the non-cancerous tissues respectively. Overexpression of β2-AR and PCBP2 was associated with advanced tumor stage and significantly worsened prognosis in patients with PDAC. Our results elucidate a new molecular mechanism by which β2-AR signaling facilitates PDAC progression through triggering PCBP2-dependent c-myc expression.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province 226001, China; Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Hua
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu Province 226001, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Chen
authors.affiliation: National Engineering Lab of Food Storage and Transportation, Nanjing University of Finance and Economics, Nanjing, Jiangsu Province 210023, China.
authors.forename: Yinji
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu Province 226001, China.
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China. Electronic address: zhougx@ntu.edu.cn.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province 226001, China. Electronic address: Shen_aiguo@yahoo.com.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D047368:Tumor Burden
chemical_list: C553443:ADRB2 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; C489427:MYC protein, human; C501903:PCBP2 protein, human; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D018343:Receptors, Adrenergic, beta-2
keywords: PCBP2; Pancreatic cancer; Proliferation; c-myc; β2-AR