Regulatory signaling in pancreatic organogenesis. implications for aberrant signaling in pancreatic cancer

Catherine Carrière, Murray Korc

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter focuses on five major embryonic signaling networks and discusses the role of their aberrant reactivation in the pathobiology of pancreatic cancer. One of the earliest signaling pathways known to be important in pancreas development is the Notch pathway. Once the transmembrane Notch receptor is activated by binding of its ligands Delta and Serrate, its intracellular domain translocates in the nucleus where it associates with recombination signal binding proteins (RBPs), also known as CSL/CBF1/Su(H)/LAG-1 transcription factors. RBP-j is a part of the trimeric transcription factor Ptf1, which is essential for early pancreas development as well as differentiation and maintenance of exocrine cells. Ptf1 is composed of p48, a pancreas- and cerebellum-specific factor, a class A bHLH protein, and RBP-j. Sonic hedgehog (Shh) and its receptors are highly expressed in the embryonic foregut before any budding of the pancreas. By embryonic day 8, Shh expression is downregulated in the region fated to give rise to the dorsal bud of the pancreas. Shh downregulation would be the key event in restricting the zone of Pdx1 expression that will become the pancreas. The Hedgehog (Hh) signaling pathway is dramatically upregulated during the progression from pancreatic intraepithelial neoplasia (PanIN) lesions to pancreatic ductal adenocarcinoma (PDAC), and PTCH expression is also present in the stromal elements adjacent to the cancer. Transforming growth factor-beta (TGFβ) isoforms are major regulators of pancreatic endocrine and exocrine cell fates, and all three isoforms and their signaling components are expressed in the pancreatic epithelium and surrounding mesenchyme from embryonic to adult stages. The TGFβ superfamily of secreted growth factors consists of several sub-families that include the three mammalian TGFβ isoforms, the activins/inhibins and the bone morphogenetic proteins (BMP).

Original languageEnglish (US)
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Pages2611-2620
Number of pages10
Volume3
ISBN (Print)9780123741455
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Organogenesis
Pancreatic Neoplasms
Pancreas
Transforming Growth Factor beta
Carrier Proteins
Protein Isoforms
Genetic Recombination
Transcription Factors
Notch Receptors
Basic Helix-Loop-Helix Transcription Factors
Activins
Inhibins
Bone Morphogenetic Proteins
Down-Regulation
Inhibin-beta Subunits
Intercellular Signaling Peptides and Proteins
Endocrine Cells
Mesoderm
Ligands
Cerebellum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Carrière, C., & Korc, M. (2010). Regulatory signaling in pancreatic organogenesis. implications for aberrant signaling in pancreatic cancer. In Handbook of Cell Signaling, 2/e (Vol. 3, pp. 2611-2620). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-374145-5.00310-7

Regulatory signaling in pancreatic organogenesis. implications for aberrant signaling in pancreatic cancer. / Carrière, Catherine; Korc, Murray.

Handbook of Cell Signaling, 2/e. Vol. 3 Elsevier Inc., 2010. p. 2611-2620.

Research output: Chapter in Book/Report/Conference proceedingChapter

Carrière, C & Korc, M 2010, Regulatory signaling in pancreatic organogenesis. implications for aberrant signaling in pancreatic cancer. in Handbook of Cell Signaling, 2/e. vol. 3, Elsevier Inc., pp. 2611-2620. https://doi.org/10.1016/B978-0-12-374145-5.00310-7
Carrière, Catherine ; Korc, Murray. / Regulatory signaling in pancreatic organogenesis. implications for aberrant signaling in pancreatic cancer. Handbook of Cell Signaling, 2/e. Vol. 3 Elsevier Inc., 2010. pp. 2611-2620
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