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LMW-PTP modulates glucose metabolism in cancer cells

Giulia Lori1, Tania Gamberi1, Paolo Paoli1

  • 1Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Biochimica Et Biophysica Acta. General Subjects
|September 26, 2018
PubMed
Abstract

Insights

Low Molecular Weight Phosphotyrosine Protein Phosphatase (LMW-PTP) regulates glucose metabolism in aggressive melanoma. Silencing LMW-PTP enhances glycolysis and alters key metabolic enzymes like PKM2.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Low Molecular Weight Phosphotyrosine Protein Phosphatase (LMW-PTP) is implicated in tumor progression and type 2 diabetes.
  • LMW-PTP interacts with receptor tyrosine kinases (RTKs) and cSrc, but studies often use cell lines with low LMW-PTP expression.
  • This study investigates LMW-PTP's role in aggressive tumors with high phosphatase expression.

Purpose of the Study:

  • To identify novel LMW-PTP substrates in aggressive human tumors.
  • To elucidate the function of LMW-PTP in cancer cell metabolism.
  • To understand the impact of LMW-PTP on glucose metabolism and related pathways.

Main Methods:

  • Proteomic analysis of A375 human melanoma cells with silenced LMW-PTP.
  • Two-dimensional electrophoresis (2-DE) and western blot using anti-phosphotyrosine antibodies.
  • Assessment of lactate production and oxygen consumption to evaluate metabolic flux.

Main Results:

  • Proteomic analysis revealed LMW-PTP substrates primarily in glycolytic metabolism (e.g., α-enolase, PKM2).
  • LMW-PTP silencing increased glycolytic flux and decreased oxidative metabolism.
  • LMW-PTP affects pyruvate kinase M2 (PKM2) tyrosine phosphorylation, nuclear localization, and activity.

Conclusions:

  • Tumor cells undergo metabolic reprogramming upon LMW-PTP silencing, enhancing glycolysis.
  • This enhanced glycolysis likely compensates for inhibited mitochondrial metabolism.
  • LMW-PTP plays a significant role in regulating glucose metabolism in melanoma cells.
Keywords:
Glucose metabolismLMW-PTPMetabolic reprogramming of cancer cellsPKM2

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