Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma

Dan Zhang1, Peng Zhang2, Pengbo Yang1

  • 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17 Section 3, People's South Road, Chengdu, 610041 People's Republic of China.

Clinical Proteomics
|May 10, 2017
PubMed
Abstract

Insights

The Na+/K+-ATPase α1 subunit (ATP1A1) is decreased in renal cell carcinoma (RCC) and acts as a tumor suppressor. Higher ATP1A1 expression correlates with better patient survival, inhibiting RCC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aberrant Na+/K+-ATPase α1 subunit (ATP1A1) expression is linked to various cancers.
  • The specific role of ATP1A1 in renal cell carcinoma (RCC) progression remains unclear.

Purpose of the Study:

  • To investigate ATP1A1 expression and its functional significance in RCC.
  • To elucidate the molecular mechanisms underlying ATP1A1's role in renal cancer.

Main Methods:

  • Quantitative proteomics (LC-MS/MS) and immunohistochemistry were used to assess ATP1A1 expression in 80 RCC and adjacent non-tumor tissues.
  • Cellular assays (CCK-8, Boyden chamber, flow cytometry) measured proliferation, migration, and apoptosis.
  • Reactive oxygen species (ROS) production and the Raf/MEK/ERK pathway were analyzed.

Main Results:

  • ATP1A1 expression was significantly decreased in RCC tissues compared to non-tumor tissues.
  • Positive ATP1A1 expression in RCC patients correlated with longer overall survival.
  • Overexpression of ATP1A1 inhibited RCC cell proliferation and migration, increased ROS production, and suppressed the Raf/MEK/ERK pathway, promoting apoptosis.

Conclusions:

  • ATP1A1 acts as a suppressor protein in renal cell carcinoma.
  • Decreased ATP1A1 expression is associated with RCC progression and poorer prognosis.
  • ATP1A1 represents a potential therapeutic target for renal cancer.

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