Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review
Although the vast majority of cancers affecting the human pancreas are pancreatic ductal adenocarcinomas (PDAC), there are several other cancer types originating from non-exocrine cells of this organ, i.e., pancreatic neuroendocrine tumors (panNET). Genomic analyses of PDAC and panNET revealed that...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1511348/full |
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| author | Hendrik Ungefroren Hendrik Ungefroren Harpal Randeva Hendrik Lehnert Jörg Schrader Jens-Uwe Marquardt Björn Konukiewitz Ralf Hass |
| author_facet | Hendrik Ungefroren Hendrik Ungefroren Harpal Randeva Hendrik Lehnert Jörg Schrader Jens-Uwe Marquardt Björn Konukiewitz Ralf Hass |
| author_sort | Hendrik Ungefroren |
| collection | DOAJ |
| description | Although the vast majority of cancers affecting the human pancreas are pancreatic ductal adenocarcinomas (PDAC), there are several other cancer types originating from non-exocrine cells of this organ, i.e., pancreatic neuroendocrine tumors (panNET). Genomic analyses of PDAC and panNET revealed that certain signaling pathways such as those triggered by transforming growth factor-β (TGF-β) are frequently altered, highlighting their crucial role in pancreatic tumor development. In PDAC, TGF-β plays a dual role acting as a tumor suppressor in healthy tissue and early stages of tumor development but as a promoter of tumor progression in later stages. This peptide growth factor acts as a potent inducer of epithelial-to-mesenchymal transition (EMT), a developmental program that transforms otherwise stationary epithelial cells to invasive mesenchymal cells with enhanced metastatic potential. TGF-β signals through both the canonical Smad pathway involving the receptor-regulated Smad proteins, SMAD2 and SMAD3, and the common-mediator Smad, SMAD4, as well as Smad-independent pathways, i.e., ERK1/2, PI3K/AKT, and somatostatin (SST). Accumulating evidence indicates an intimate crosstalk between TGF-β and SST signaling, not only in PDAC but, more recently, also in panNET. In this work, we review the available evidence on signaling interactions between both pathways, which we believe are of potential but as yet insufficiently appreciated importance for pancreatic cancer development and/or progression as well as novel therapeutic approaches. |
| format | Article |
| id | doaj-art-a7545c14ac474da5bdb10aa65dab1870 |
| institution | OA Journals |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-a7545c14ac474da5bdb10aa65dab18702025-08-20T01:57:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-03-011610.3389/fendo.2025.15113481511348Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief reviewHendrik Ungefroren0Hendrik Ungefroren1Harpal Randeva2Hendrik Lehnert3Jörg Schrader4Jens-Uwe Marquardt5Björn Konukiewitz6Ralf Hass7Institute of Pathology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, GermanyFirst Department of Medicine, University Hospital Schleswig-Holstein (UKSH), Campus Lübeck, Lübeck, GermanyUniversity Hospital of Coventry and Warwickshire (UHCW) and Warwick Medical School, Coventry, United KingdomUniversity Hospital of Coventry and Warwickshire (UHCW) and Warwick Medical School, Coventry, United KingdomFirst Department of Medicine, Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, GermanyFirst Department of Medicine, University Hospital Schleswig-Holstein (UKSH), Campus Lübeck, Lübeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, GermanyBiochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, GermanyAlthough the vast majority of cancers affecting the human pancreas are pancreatic ductal adenocarcinomas (PDAC), there are several other cancer types originating from non-exocrine cells of this organ, i.e., pancreatic neuroendocrine tumors (panNET). Genomic analyses of PDAC and panNET revealed that certain signaling pathways such as those triggered by transforming growth factor-β (TGF-β) are frequently altered, highlighting their crucial role in pancreatic tumor development. In PDAC, TGF-β plays a dual role acting as a tumor suppressor in healthy tissue and early stages of tumor development but as a promoter of tumor progression in later stages. This peptide growth factor acts as a potent inducer of epithelial-to-mesenchymal transition (EMT), a developmental program that transforms otherwise stationary epithelial cells to invasive mesenchymal cells with enhanced metastatic potential. TGF-β signals through both the canonical Smad pathway involving the receptor-regulated Smad proteins, SMAD2 and SMAD3, and the common-mediator Smad, SMAD4, as well as Smad-independent pathways, i.e., ERK1/2, PI3K/AKT, and somatostatin (SST). Accumulating evidence indicates an intimate crosstalk between TGF-β and SST signaling, not only in PDAC but, more recently, also in panNET. In this work, we review the available evidence on signaling interactions between both pathways, which we believe are of potential but as yet insufficiently appreciated importance for pancreatic cancer development and/or progression as well as novel therapeutic approaches.https://www.frontiersin.org/articles/10.3389/fendo.2025.1511348/fullTGF-βsomatostatinsignalingpancreaspancreatic ductal adenocarcinomaneuroendocrine tumors |
| spellingShingle | Hendrik Ungefroren Hendrik Ungefroren Harpal Randeva Hendrik Lehnert Jörg Schrader Jens-Uwe Marquardt Björn Konukiewitz Ralf Hass Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review Frontiers in Endocrinology TGF-β somatostatin signaling pancreas pancreatic ductal adenocarcinoma neuroendocrine tumors |
| title | Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review |
| title_full | Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review |
| title_fullStr | Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review |
| title_full_unstemmed | Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review |
| title_short | Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review |
| title_sort | crosstalk of tgf β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas a brief review |
| topic | TGF-β somatostatin signaling pancreas pancreatic ductal adenocarcinoma neuroendocrine tumors |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1511348/full |
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