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Pelullo M, Zema S, Nardozza F, et al. Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer. Front Genet. 2019;10:711doi: 10.3389/fgene.2019.00711.
Pelullo, M., Zema, S., Nardozza, F., Checquolo, S., Screpanti, I., & Bellavia, D. (2019). Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer. Frontiers in genetics, 10711. https://doi.org/10.3389/fgene.2019.00711
Pelullo, Maria, et al. "Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer." Frontiers in genetics vol. 10 (2019): 711. doi: https://doi.org/10.3389/fgene.2019.00711
Pelullo M, Zema S, Nardozza F, Checquolo S, Screpanti I, Bellavia D. Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer. Front Genet. 2019 Aug 21;10:711. doi: 10.3389/fgene.2019.00711. eCollection 2019. PMID: 31552081; PMCID: PMC6736567.
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Front Genet. 2019 Aug 21;10:711. doi: 10.3389/fgene.2019.00711. eCollection 2019.

Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer.

Frontiers in genetics

Maria Pelullo, Sabrina Zema, Francesca Nardozza, Saula Checquolo, Isabella Screpanti, Diana Bellavia

Affiliations

  1. Center of Life Nano Science Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
  2. Department of Molecular Medicine, Sapienza University, Rome, Italy.
  3. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.

PMID: 31552081 PMCID: PMC6736567 DOI: 10.3389/fgene.2019.00711

Abstract

Constitutive activation of the Hedgehog (Hh) signaling pathway is associated with increased risk of developing several malignancies. The biological and pathogenic importance of Hh signaling emphasizes the need to control its action tightly, both physiologically and therapeutically. Evidence of crosstalk between Hh and other signaling pathways is reported in many tumor types. Here, we provide an overview of the current knowledge about the communication between Hh and major signaling pathways, such as Notch, Wnt, and transforming growth factor β (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 tumors, at the same time. Therefore, starting from a plethora of stimuli that activate multiple signaling pathways, we describe the signals that preferentially converge on the Hh signaling cascade that influence its activity. Moreover, we highlight several connection points between Hh and Notch, Wnt, or TGF-β pathways, showing a reciprocal synergism that contributes to tumorigenesis, supporting a more malignant behavior by tumor cells, such as in leukemia and brain tumors. Understanding the importance of these molecular interlinking networks will provide a rational basis for combined anticancer drug development.

Keywords: Hedgehog; Notch; TGF-β; Wnt; signaling pathway; tumorigenesis

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