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HER2 and Src co-regulate proliferation, migration and transformation by downstream signaling pathways in

Qing Zhou1, Peiyu Jin, Jieyu Liu

  • 1Department of Environmental and Occupational Health, Liaoning Provincial Key Laboratory of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, P. R. China. 1948510918@qq.com 1101246743@qq.com 304067542@qq.com 53366583@qq.com shxi@cmu.edu.cn.

Metallomics : Integrated Biometal Science
|August 2, 2018
PubMed

Insights

Arsenic exposure in drinking water may cause bladder cancer by increasing HER2 and Src signaling. Inhibiting these proteins reduced cell growth and migration, suggesting a key role in arsenic-induced cell transformation.

Area of Science:

  • Oncology
  • Environmental Health
  • Molecular Biology

Background:

  • Epidemiological studies link arsenic in drinking water to increased bladder cancer risk in endemic areas.
  • Elevated Human Epidermal growth factor Receptor 2 (HER2) expression is common in various human cancers, including bladder cancer.

Purpose of the Study:

  • To investigate the role of HER2 in arsenite-induced uroepithelial cell transformation.
  • To explore the involvement of Src family kinases in HER2 signaling during arsenite exposure.

Main Methods:

  • Chronic arsenite exposure of SV-HUC-1 uroepithelial cells.
  • Analysis of HER2, Src, and downstream signaling pathway activation (Ras/Raf/MAPK, PI3K/AKT, JAK2/STAT3).
  • Assessment of proliferation factors (cyclin D1, COX2, PCNA, VEGF, HIF-1α).
  • Evaluation of cell growth and migration following HER2 inhibition or knockdown, and Src inhibition.

Main Results:

  • Chronic arsenite exposure increased HER2 and Src expression in a time-dependent manner.
  • Arsenite upregulated proliferation factors and activated multiple signaling pathways (Ras/Raf/MAPK, PI3K/AKT, JAK2/STAT3).
  • HER2 inhibition/knockdown and Src inhibition suppressed arsenite-induced signaling, cell growth, and migration, indicating an interaction between HER2 and Src.

Conclusions:

  • HER2 and Src family kinases play a critical role in arsenite-induced uroepithelial cell transformation.
  • Arsenite likely promotes bladder cancer development through HER2/Src-mediated activation of multiple downstream signaling pathways.

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