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Notch increased vitronection adhesion protects myeloma cells from drug induced apoptosis

Yurun Ding1, Yi Shen1

  • 1Department of Orthopaedic, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University 1630 Dong Fang Road, Shanghai 200127, China.

Biochemical and Biophysical Research Communications
|October 24, 2015
PubMed

Insights

Notch signaling promotes multiple myeloma drug resistance by upregulating integrin αvβ5, enhancing cell adhesion to vitronectin. Blocking this pathway offers a promising new strategy for treating drug-resistant myeloma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Notch signaling is implicated in various cancers, including multiple myeloma.
  • Notch signaling contributes to chemotherapy resistance in myeloma cells, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which Notch signaling contributes to drug resistance in multiple myeloma.
  • To investigate the role of integrin αvβ5 and vitronectin adhesion in Notch-mediated drug resistance.

Main Methods:

  • Utilized siRNA to silence Notch-1 receptor expression.
  • Employed integrin αvβ5 blocking antibodies.
  • Assessed myeloma cell adhesion to vitronectin.
  • Evaluated drug-induced apoptosis in myeloma cells.

Main Results:

  • Notch signaling activation up-regulated integrin αvβ5 expression in myeloma cells.
  • Silencing Notch-1 or blocking integrin αvβ5 reduced myeloma cell adhesion to vitronectin.
  • Vitronectin-mediated cell adhesion conferred protection against drug-induced apoptosis.

Conclusions:

  • Notch signaling promotes multiple myeloma drug resistance through upregulation of integrin αvβ5 and enhanced vitronectin adhesion.
  • This novel mechanism links Notch signaling, vitronectin adhesion, and drug resistance in multiple myeloma.
  • Targeting the αvβ5 integrin receptor presents a potential therapeutic strategy for overcoming drug resistance in multiple myeloma.
Keywords:
AdhesionDrug resistanceIntegrin αvβ5Multiple myelomaNotchVitronectin

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