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Collagen/β1 integrin signaling up-regulates the ABCC1/MRP-1 transporter in an ERK/MAPK-dependent manner

Mohammed-Amine El Azreq1, Dalila Naci, Fawzi Aoudjit

  • 1Centre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, QC G1V 4G2, Canada.

Molecular Biology of the Cell
|July 13, 2012
PubMed

Insights

Collagen/β1 integrin signaling prevents chemoresistance in leukemia cells by increasing the ABCC1 transporter, which reduces doxorubicin accumulation. Targeting this pathway may overcome drug resistance.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • β1 integrins' role in cancer chemoresistance is not fully understood.
  • Multidrug resistance limits the efficacy of chemotherapy.

Purpose of the Study:

  • Investigate how β1 integrins influence chemoresistance in leukemia.
  • Elucidate the role of collagen/β1 integrin signaling in doxorubicin resistance.

Main Methods:

  • Utilized Jurkat and HSB2 leukemic T-cells.
  • Assessed doxorubicin intracellular content and apoptosis.
  • Examined ABCC1 transporter expression and function.
  • Investigated the involvement of ERK/MAPK and actin polymerization pathways.

Main Results:

  • Collagen/β1 integrin signaling inhibited doxorubicin-induced apoptosis.
  • This signaling pathway up-regulated ABCC1 transporter expression and function.
  • ERK/MAPK pathway activation and actin polymerization were crucial for these effects.
  • Collagen reduced intracellular doxorubicin levels by up-regulating ABCC1.

Conclusions:

  • Collagen/β1 integrin/ERK signaling enhances chemoresistance by up-regulating ABCC1.
  • ABCC1 activation is a significant pathway contributing to cancer drug resistance.
  • Combined targeting of collagen/β1 integrin and ABCC1 may improve cancer treatment efficacy.

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