Reelin and pancreatic cancer

Kimberly Walter, Michael S Goggins

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Classically, the RELN gene has been known for its role in neuronal migration and positioning during central nervous system development. Absence of RELN expression results in the characteristic reeler phenotype in rodents, marked by severe defects in cortical layer formation and an uncoordinated, unsteady gait. In humans, loss of reelin expression causes a type of lissencephaly with severe cortical and cerebellar malformation. RELN is also expressed in peripheral tissues, including the liver, kidney, adrenal glands, and pancreas, suggesting an additional role for reelin in development and possibly in structural maintenance of these organs (Smalheiser et al., 2000). Recent findings indicate that RELN is expressed in the normal duct cells of the adult pancreas, and that RELN expression is frequently lost in pancreatic ductal adenocarcinomas and in precursor neoplasms in association with epigenetic silencing (Sato et al., 2006). In vitro studies suggest that loss of RELN contributes to the ability of pancreatic cancer cells to migrate and invade surrounding tissues. These findings support the notion that the effect of reelin pathway status on cell migration may depend on the cell type affected, perhaps depending on the downstream effects of reelin-mediated signaling on the cell's cytoskeleton. for example, reelin loss stimulates migration in some cell types (Gong et al., 2007), even though the phenotype of RELN gene inactivation in the brain is a failure of migration (Kim et al., 2002; Trommsdorff et al., 1999). Although epigenetic mechanisms appear to be responsible for RELN silencing in pancreatic neoplasms, the mechanism directing this epigenetic silencing of RELN expression is uncertain (Sato et al., 2006).

Original languageEnglish (US)
Title of host publicationReelin Glycoprotein: Structure, Biology and Roles in Health and Disease
PublisherSpringer New York
Pages421-430
Number of pages10
ISBN (Print)9780387767611, 9780387767604
DOIs
StatePublished - 2008

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ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

Cite this

Walter, K., & Goggins, M. S. (2008). Reelin and pancreatic cancer. In Reelin Glycoprotein: Structure, Biology and Roles in Health and Disease (pp. 421-430). Springer New York. https://doi.org/10.1007/978-0-387-76761-1_28