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AXL phosphorylates and up-regulates TNS2 and its implications in IRS-1-associated metabolism in cancer cells

Li-Chun Cheng1,2, Yen-Lin Chen3, An-Ning Cheng2

  • 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

Journal of Biomedical Science
|November 14, 2018
PubMed
Abstract

Insights

The receptor tyrosine kinase Axl phosphorylates TNS2, impacting glucose metabolism in pancreatic cancer. This Axl/TNS2/IRS-1 signaling pathway influences key enzymes like Glut4 and PDK1, crucial for cancer cell growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Metabolism

Background:

  • TNS2 (Tensin 2) is a focal adhesion protein interacting with receptor tyrosine kinases like Axl.
  • The precise interaction between TNS2 and Axl, and its role in signaling pathways such as IRS-1, remains unclear.
  • Understanding these interactions is vital for elucidating mechanisms in pancreatic cancer.

Purpose of the Study:

  • To investigate the interaction between TNS2 and Axl.
  • To confirm the relationship between TNS2 expression and key signaling molecules (Axl, IRS-1, PDK1, Glut4) in pancreatic cancer.
  • To explore the role of Axl/TNS2 signaling in glucose metabolism within cancer cells.

Main Methods:

  • Western blot and IP-Western blot assays were used to measure protein expression levels.
  • Human pancreatic cancer and non-cancer tissues from 33 patients were analyzed using tissue microarrays.
  • Enzyme-linked immunohistochemistry assays and statistical analyses (Pearson's chi-square, t-test) were employed to assess marker expression and relationships.

Main Results:

  • TNS2 was identified as a direct phosphorylation substrate of Axl.
  • A positive correlation was observed between TNS2 expression and the expression of Axl, IRS-1, PDK1, and Glut4 in pancreatic cancer patients.
  • Axl appears to modulate glucose metabolism via TNS2 and IRS-1, up-regulating aerobic glycolysis enzymes Glut4 and PDK1.

Conclusions:

  • Axl directly binds to and phosphorylates TNS2, establishing a novel interaction.
  • The Axl/TNS2/IRS-1 signaling axis plays a significant role in regulating glucose metabolism in pancreatic cancer cells.
  • This cross-talk mechanism highlights a potential therapeutic target for pancreatic cancer treatment.
Keywords:
AxlC1-TENGlucose metabolismGlut4IRS1PDK1Pancreatic cancerTensin2

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