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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00711

Wnt, Notch and TGFβ pathways impinge on Hedgehog signalling complexity: an open window on cancer

 Maria Pelullo1*, Sabrina Zema2, Francesca Nardozza3,  Saula Checquolo4,  Isabella Screpanti5 and  Diana Bellavia5*
  • 1Center for Life NanoScience (IIT), Italy
  • 2Sapienza University of Rome, Italy
  • 3Department of Molecular Medicine/Laboratory of Molecular Pathology, Sapienza University of Rome, Italy
  • 4Department of Medical and Surgical Sciences and Biotechnology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Italy
  • 5Department of Molecular Medicine, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Italy

Constitutive activation of the Hh signalling pathway is associated with increased risk of developing several malignancies. The biological and pathogenic importance of Hh signalling emphasizes the need to control its action tightly, both physiologically and therapeutically. Evidence of crosstalk between Hh and other signalling pathways is reported in many tumour types. Here, we provide an overview of the current knowledge about the communication between Hh and major signalling pathways, such as Notch, Wnt and TGF/β, which play critical roles in both embryonic and adult life. When these pathways are unbalanced, impaired crosstalk contributes to disease development. It is reported that more than one of these pathways are active in different type of tumours, at the same time. Therefore, starting from a plethora of stimuli that activate multiple signalling pathways, we describe the signals that preferentially converge on the Hh signalling cascade that influence its activity. Moreover, we highlight several connection points between Hh and Notch, Wnt or TGFβ pathways, showing a reciprocal synergism that contributes to tumorigenesis, supporting a more malignant behaviour by tumour cells, such as in leukaemia and brain tumours. Understanding the importance of these molecular interlinking networks will provide a rational basis for combined anticancer drug development.

Keywords: Notch, Wnt, TGFβ, Signalling pathway, tumorigenesis, Hedgehog

Received: 13 Mar 2019; Accepted: 05 Jul 2019.

Edited by:

William Cho, Queen Elizabeth Hospital (QEH), Hong Kong

Reviewed by:

Bradley W. Doble, McMaster University, Canada
Paola Rizzo, University of Ferrara, Italy  

Copyright: © 2019 Pelullo, Zema, Nardozza, Checquolo, Screpanti and Bellavia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Maria Pelullo, Center for Life NanoScience (IIT), Rome, Italy, Maria.Pelullo@iit.it
Prof. Diana Bellavia, Department of Molecular Medicine, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Roma, 00185, Lazio, Italy, diana.bellavia@uniroma1.it