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Exogenous bacterial DnaK increases protein kinases activity in human cancer cell lines

Francesca Benedetti1, Sabrina Curreli2, Robert C Gallo2

  • 1Institute of Human Virology and Global Virus Network Center, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Journal of Translational Medicine
|February 10, 2021
PubMed
Abstract

Insights

Mycoplasma DnaK protein disrupts cancer cell signaling by altering kinase activity, potentially driving cancer progression. This finding reveals a new mechanism for how the human microbiota influences cancer development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Microbiology

Background:

  • Kinases play a critical role in cancer cell signaling, regulating pathways involved in carcinogenesis and progression.
  • The human microbiota, including Mycoplasmas, is increasingly recognized for its influence on cancer development and treatment outcomes.
  • Mycoplasmas and their proteins are present in the tumor microenvironment and linked to cellular transformation.

Purpose of the Study:

  • To investigate the impact of Mycoplasma DnaK on kinase activity in various cancer cell lines.
  • To elucidate the role of bacterial proteins from the human microbiota in cancer signaling.

Main Methods:

  • Treatment of four eukaryotic cancer cell lines (lung, prostate, colon adenocarcinoma, neuroblastoma) with exogenous Mycoplasma DnaK.
  • Measurement of kinase and specific substrate phosphorylation at 20 and 60 minutes post-treatment.
  • Kinome analysis to assess global kinase activity changes.

Main Results:

  • Mycoplasma DnaK significantly dysregulates the activity of specific kinases and their substrates.
  • These affected kinases and substrates are known to be involved in carcinogenesis and cancer progression.
  • The study identified a novel mechanism of kinase dysregulation mediated by bacterial proteins.

Conclusions:

  • Mycoplasma DnaK alters host cell phosphorylation, contributing to cancer progression.
  • Bacterial components within the tumor microenvironment can deregulate critical cellular signaling pathways.
  • This research highlights a new pathway through which the human microbiota impacts cancer.
Keywords:
CancerDnaKKinaseMycoplasmaPhosphorylation

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