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Targeting PTEN in Colorectal Cancers

  • Larissa Kotelevets
  • Mark G. H. Scott
  • Eric ChastreEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1110)

Abstract

Phosphatase and tensin homolog (PTEN) is a tumour suppressor that represents one of the most common targets for genetic defect in human cancer. PTEN controls an array of physiopathological processes related to cell proliferation, differentiation, DNA/chromosome integrity, apoptosis and invasiveness. PTEN dephosphorylates not only proteins, but also phosphoinositides generated by phosphatidylinositol 3-kinase, thus counteracting the Akt signalling pathway. Interestingly, PTEN can also exert some biological functions independently of its catalytic activity.

A feature of colorectal cancers is the relatively low incidence of PTEN mutation or deletion, whereas PTEN downregulation occurs in approximately one third of tumours. PTEN inactivation may be even higher when changes in posttranslational modifications and/or mislocalization of the tumour suppressor are accounted for. Strategies based on pharmacologically-induced restoration of wild-type PTEN function in colon cancer cells could therefore be considered, to impact cell growth, trigger apoptosis, and sensitize tumour cells to therapeutic agents.

This review details current knowledge of the mechanisms regulating PTEN expression, activity and function. It also focuses on the use of small molecules targeting positive or negative PTEN regulators and summarizes alternative strategies that could be used to alter PTEN conformation/activity. Finally, we propose an outline of a personalized approach to restore PTEN function in colon cancer cells.

Keywords

AKT signaling DNA repair Molecular scaffolds Phosphatase Tumor suppressor 

Notes

Acknowledgements

This work was supported by the Centre National de la Recherche Scientifique and Institut National de la Santé et de la Recherche Médicale. Work in the group of MGHS is also supported by the Ligue Contre le Cancer (comité de l’Oise) and the Who am I? laboratory of excellence (grant ANR-11-LABX-0071) funded by the “Investments for the Future” program operated by The French National Research Agency (grant ANR-11-IDEX-0005-01).

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Larissa Kotelevets
    • 1
    • 2
  • Mark G. H. Scott
    • 3
    • 4
  • Eric Chastre
    • 1
    • 2
    Email author
  1. 1.Inserm, UMR S 938, Cancer Biology and TherapeuticsCentre de Recherche Saint-AntoineParisFrance
  2. 2.Hôpital Saint-Antoine, Site Bâtiment Kourilsky, Université Pierre-et-Marie-Curie Paris 6Sorbonne UniversitésParisFrance
  3. 3.U1016, Institut Cochin, 27, CNRS, UMR8104Institut National de la Santé et de la RechercheMédicaleParisFrance
  4. 4.Université Paris DescartesSorbonne Paris CitéParisFrance

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