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HER4 promotes cell survival and chemoresistance in osteosarcoma via interaction with NDRG1

Hongsheng Wang1, Wei Sun2, Mengxiong Sun2

  • 1Department of Orthopedics, Shanghai General Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China; Department of Orthopedics, Yangpu Hospital, Tongji University, Shanghai, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|March 11, 2018
PubMed

Insights

HER4 and NDRG1 proteins are crucial for osteosarcoma (OS) cell survival and chemotherapy resistance. Targeting these proteins may offer new therapeutic strategies for treating this common childhood bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Osteosarcoma (OS) is the most frequent primary bone malignancy in children and adolescents.
  • Chemotherapy resistance significantly hinders effective OS treatment.
  • Understanding the mechanisms of OS cell survival during chemotherapy is critical.

Purpose of the Study:

  • To investigate the role of HER4 expression in osteosarcoma.
  • To elucidate the mechanisms by which HER4 influences OS cell survival and chemoresistance.
  • To explore the potential of HER4 and NDRG1 as therapeutic targets in OS.

Main Methods:

  • Immunohistochemistry was used to assess HER4 expression in OS tissues.
  • HER4 knockdown was performed using shRNA in vitro and in vivo.
  • Cellular responses to stress conditions and interactions between HER4 and NDRG1 were analyzed.

Main Results:

  • HER4 expression correlated with OS tumor characteristics and patient survival.
  • HER4 knockdown inhibited OS cell growth, induced senescence and apoptosis, and increased sensitivity to stress.
  • HER4 interacts with NDRG1, which can counteract HER4 knockdown effects in stressed conditions.

Conclusions:

  • HER4 plays a significant role in OS cell survival and chemoresistance, particularly under adverse conditions.
  • The interaction between HER4 and NDRG1 is important for OS cell survival.
  • HER4 and NDRG1 represent potential therapeutic targets for osteosarcoma treatment.
Keywords:
Cell growthChemotherapy resistanceHER4NDRG1Osteosarcoma

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