Modelling the microtubule: towards a better understanding of short-chain fatty acid molecular pharmacology

Josephine Kilner1, Bernard M Corfe, Stephen J Wilkinson

  • 1Department of Chemical and Biological Engineering, ChELSI Institute, The University of Sheffield, Sheffield, UK.

Molecular Biosystems
|February 2, 2011
PubMed

Insights

Short-chain fatty acids (SCFAs), acting as histone deacetylase inhibitors, disrupt microtubule (MT) function in colon cancer cells by altering tubulin isotypes. Systems biology models can reveal novel therapeutic strategies for cancer prevention and treatment.

Area of Science:

  • Systems biology
  • Cancer research
  • Molecular biology

Background:

  • Short-chain fatty acids (SCFAs) are chemopreventive compounds produced in the colon.
  • SCFAs impair microtubule (MT) function in colon cancer cells by altering β-tubulin isotype expression.
  • The "tubulin code" influences MT-associated proteins, kinesins, and post-transcriptional modifications (PTMs), affecting cellular functions.

Purpose of the Study:

  • To review how SCFAs, as histone deacetylase inhibitors (HDACi's), affect tubulin dynamics, modifications, and isotypes.
  • To explore the role of systems biology in understanding SCFA-mediated disruption of cytoskeletal function.
  • To propose novel therapeutic strategies for cancer prevention and treatment.

Main Methods:

  • Review of existing literature on SCFAs, tubulin, MT dynamics, and systems biology.
  • Analysis of mechanistic models describing tubulin-MT structure and dynamics.
  • Integration of models for transcription and cell cycle regulation.

Main Results:

  • SCFAs, functioning as HDACi's, promote protein acetylation, including histones and cytoskeletal proteins.
  • Alterations in β-tubulin isotype composition by SCFAs impact MT function and the "tubulin code".
  • Disruption of the MT cytoskeleton is a key target for cancer therapies.

Conclusions:

  • Systems biology approaches, integrating experimental data and computational models, are crucial for understanding SCFA effects on cytoskeletal function.
  • Mechanistic models can generate hypotheses for how SCFAs disrupt cellular processes in colon cancer.
  • Developing and elaborating these models offers potential for novel cancer therapies.

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