Smad4-TGF-ß signaling pathways in pancreatic cancer pathogenesis

Murray Korc

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a 9% 5-yearsurvival rate. For reasons that are not readily evident, KRAS is mutated in90-95% of PDAC cases, and this truncal alteration is associated with a highfrequency of mutations in crucially important tumor suppressor genes, mostnotably CDKN2A (~90%), a gene that encodes p16, TP53 (~70%), and SMAD4(~50%). Concomitantly, there is overexpression of transforming growth factorbeta (TGF-ß) isoforms and of high-affinity tyrosine kinase receptors (TKRs)and their ligands. Enhanced cancer cell proliferation and migration mediated byTKRs, combined with loss of beneficial TGF-ß-dependent pathways required torestrain uncontrolled cell proliferation, contributes to PDAC's biological aggressiveness. This chapter provides an overview of these issues and focuses on therole of alterations in Smad4 expression and function and aberrant TGF-ß signalingthat combine to promote pancreatic cancer growth through cell autonomousand paracrine actions, thereby contributing in an important manner to PDACpathobiology.

Original languageEnglish (US)
Title of host publicationPancreatic Cancer
PublisherSpringer New York
Pages431-455
Number of pages25
ISBN (Electronic)9781493971930
ISBN (Print)9781493971916
DOIs
StatePublished - Apr 11 2018

Fingerprint

Pancreatic Neoplasms
Growth
Adenocarcinoma
Cell Proliferation
p16 Genes
Receptor Protein-Tyrosine Kinases
Tumor Suppressor Genes
Cell Movement
Neoplasms
Protein Isoforms
Ligands
Mutation

Keywords

  • Angiogenesis
  • Canonical signaling
  • Non-canonical signaling
  • Pancreatic cancer
  • Smad4
  • Smad7
  • TGF-ß
  • TGF-ß
  • Tumor microenvironment

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Korc, M. (2018). Smad4-TGF-ß signaling pathways in pancreatic cancer pathogenesis. In Pancreatic Cancer (pp. 431-455). Springer New York. https://doi.org/10.1007/978-1-4939-7193-0_17

Smad4-TGF-ß signaling pathways in pancreatic cancer pathogenesis. / Korc, Murray.

Pancreatic Cancer. Springer New York, 2018. p. 431-455.

Research output: Chapter in Book/Report/Conference proceedingChapter

Korc, Murray. / Smad4-TGF-ß signaling pathways in pancreatic cancer pathogenesis. Pancreatic Cancer. Springer New York, 2018. pp. 431-455
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