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Two independent signaling pathways mediate the antiapoptotic action of macrophage-stimulating protein on epithelial

A Danilkovitch1, S Donley, A Skeel

  • 1Immunopathology Section, Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland, USA. danilkovitch@mail.ncifcrf.gov

Molecular and Cellular Biology
|February 25, 2000
PubMed

Insights

Macrophage-stimulating protein (MSP) promotes epithelial cell survival by activating PI3-K/AKT and MAPK pathways. Adhesion is crucial for MSP to utilize MAPK for survival signaling, highlighting crosstalk between cell matrix and growth factors.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Epithelial cell survival depends on growth factors and extracellular matrix interactions.
  • Macrophage-stimulating protein (MSP) acts as a growth and motility factor for epithelial cells.
  • Understanding MSP's role in cell survival is crucial for regenerative medicine and cancer research.

Purpose of the Study:

  • To investigate the effect of MSP on epithelial cell survival.
  • To elucidate the signaling pathways involved in MSP-mediated cell survival.
  • To explore the interplay between cell adhesion and MSP signaling.

Main Methods:

  • Cell culture of epithelial cells in serum-free medium.
  • Assessment of cell survival and apoptosis.
  • Pharmacological inhibition of phosphatidylinositol 3'-kinase (PI3-K)/AKT and mitogen-activated protein kinase (MAPK) pathways.
  • Analysis of MSP's effect on signaling pathway activation and cross-talk.

Main Results:

  • MSP promotes survival of both adherent and suspended epithelial cells.
  • Adherent cell survival involves both PI3-K/AKT and MAPK pathways, which function independently.
  • MSP utilizes PI3-K/AKT and MAPK pathways in adherent cells, with each pathway partially contributing to anti-apoptosis.
  • MSP's anti-apoptotic effect in suspended cells (anoikis) is solely mediated by the PI3-K/AKT pathway.
  • MAPK activation by MSP is insufficient to prevent anoikis without PI3-K/AKT pathway activity.
  • Cell adhesion is essential for MSP to engage the MAPK pathway for survival, potentially through nuclear translocation of activated MAPK.

Conclusions:

  • MSP plays a significant role in regulating epithelial cell survival through distinct signaling mechanisms.
  • The PI3-K/AKT pathway is critical for MSP-mediated survival in both adherent and suspended cells.
  • The MAPK pathway contributes to MSP-mediated survival in adherent cells, requiring cell adhesion for its function.
  • Cross-talk exists between cell-matrix adhesion and growth factor signaling (MSP) in regulating cell survival via the MAPK pathway.

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