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Fluorescence Microscopy for ATP Internalization Mediated by Macropinocytosis in Human Tumor Cells and Tumor-xenografted Mice
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Signal transduction pathways associated with ATP-induced proliferation of colon adenocarcinoma cells

Natalia Buzzi1, Ricardo Boland, Ana Russo de Boland

  • 1Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, 8000 Bahía Blanca, Argentina.

Biochimica Et Biophysica Acta
|June 22, 2010
PubMed
Abstract

Insights

Extracellular adenosine 5'-triphosphate (ATP) stimulates Caco-2 cell proliferation by activating mitogen-activated protein kinase (MAPK) cascades. This pathway involves key transcription factors and is crucial for understanding colon cancer development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Extracellular adenosine 5'-triphosphate (ATP) activates P2Y receptors on intestinal Caco-2 cells.
  • This activation leads to increased phosphorylation of ERK1/2, JNK, and p38 MAP kinases (MAPKs).

Purpose of the Study:

  • To investigate if extracellular ATP-P2Y receptor signaling pathways are necessary for Caco-2 cell proliferation.
  • To elucidate the role of MAPK cascades in ATP-induced Caco-2 cell growth.

Main Methods:

  • Confocal microscopy and immunoblotting were used to study protein localization and expression.
  • Specific inhibitors (UO126, SB203580, SP600125) were employed to block MAPK activity.

Main Results:

  • ATP stimulation caused ERK1/2 and JNK nuclear translocation, participating in transcription factor phosphorylation (JunD, ATF-1, ATF-2).
  • ATP induced c-Fos and MKP-1 expression via MAPK activation.
  • ATP significantly increased Caco-2 cell proliferation, an effect abrogated by MAPK inhibitors.

Conclusions:

  • Extracellular ATP drives Caco-2 human colonic cancer cell proliferation through MAPK activation and transcription factor modulation.
  • Understanding these ATP-mediated pathways is vital for cancer development insights and therapeutic strategy design.

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