Prostaglandins in cancer cell adhesion, migration, and invasion

David G. Menter, Raymond N. Dubois

Research output: Contribution to journalReview articlepeer-review

76 Scopus citations

Abstract

Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2), which binds to and activates G-protein-coupled prostaglandin E 1-4 receptors (EP 1-4). Selectively targeting the COX-2/mPGES-1/PGE2/ EP 1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM). Interactions with the ECM are mediated by cell surface integrins by outside-in signaling through Src and focal adhesion kinase (FAK) and/or inside-out signaling through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/ EP 1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

Original languageEnglish (US)
Article number723419
JournalInternational Journal of Cell Biology
DOIs
StatePublished - 2012
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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