Signaling Networks That Control Cellular Plasticity in Pancreatic Tumorigenesis, Progression, and Metastasis

Gastroenterology. 2019 May;156(7):2073-2084. doi: 10.1053/j.gastro.2018.12.042. Epub 2019 Feb 1.

Abstract

Pancreatic ductal adenocarcinoma is one of the deadliest cancers, and its incidence on the rise. The major challenges in overcoming the poor prognosis with this disease include late detection and the aggressive biology of the disease. Intratumoral heterogeneity; presence of a robust, reactive, and desmoplastic stroma; and the crosstalk between the different tumor components require complete understanding of the pancreatic tumor biology to better understand the therapeutic challenges posed by this disease. In this review, we discuss the processes involved during tumorigenesis encompassing the inherent plasticity of the transformed cells, development of tumor stroma crosstalk, and enrichment of cancer stem cell population during tumorigenesis.

Keywords: Cancer Stem Cells; Pancreatic Cancer Associated Fibroblasts; Pancreatic Cellular Plasticity; Signaling Crosstalk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / secondary
  • Carcinoma, Pancreatic Ductal / therapy
  • Cell Communication
  • Cell Movement
  • Cell Plasticity*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Mutation
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Phenotype
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • Inflammation Mediators