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Published on: May 18, 2018
Embryonic signaling in melanoma: potential for diagnosis and therapy
Luigi Strizzi1, Katharine M Hardy, Gina T Kirsammer
1Children’s Memorial Research Center, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 2300 Children’s Plaza, Box 222, Chicago, IL 60614, USA. lstrizzi@childrensmemorial.org
Abstract:
As the frequency of melanoma diagnosis increases, current treatment strategies are still struggling to significantly impact patient survival. Some promise has been shown in treating certain melanomas by targeting activated signaling pathways resulting from specific mutations in proteins, such as BRAF and NRAS. Recently, the identification of embryonic signaling pathways in melanoma has helped us better understand certain biological characteristics, such as cellular heterogeneity and phenotypic plasticity, and has provided novel insight pertinent to diagnosis and therapy. For instance, our studies have shown that the TGF-β family member, Nodal, is expressed in melanoma and is responsible, at least in part, for tumor cell plasticity and aggressiveness. Since the majority of normal adult tissues do not express Nodal, we reason that this embryonic morphogen could be used to identify and target aggressive melanoma cells. We have also identified that molecular cross-talk between the Notch and Nodal pathways may represent a mechanism responsible for the overexpression of Nodal in melanoma. Further exploitation of the relationship between embryonic signaling pathways and cancer pathogenesis could lead to novel approaches for diagnosis and therapy in cancers, such as melanoma.
Insights
Embryonic signaling pathways, like Nodal, are found in melanoma, driving tumor cell plasticity and aggressiveness. Targeting Nodal offers a potential strategy for identifying and treating aggressive melanoma.
Area of Science:
- Oncology
- Developmental Biology
- Cancer Signaling
Background:
- Melanoma diagnosis rates are rising, yet survival rates remain suboptimal.
- Targeting mutated signaling pathways (e.g., BRAF, NRAS) shows promise for melanoma treatment.
- Embryonic signaling pathways are increasingly recognized for their role in melanoma biology.
Purpose of the Study:
- To investigate the role of embryonic signaling pathways in melanoma pathogenesis.
- To explore Nodal as a potential therapeutic target for aggressive melanoma.
- To understand the interplay between Notch and Nodal pathways in melanoma.
Main Methods:
- Analysis of Nodal expression in melanoma tissues.
- Investigating the functional role of Nodal in melanoma cell plasticity and aggressiveness.
- Examining molecular cross-talk between Notch and Nodal signaling pathways.
Main Results:
- Nodal, a TGF-β family member, is expressed in melanoma.
- Nodal contributes to melanoma cell plasticity and aggressiveness.
- Cross-talk between Notch and Nodal pathways may cause Nodal overexpression in melanoma.
Conclusions:
- Nodal's expression in melanoma, unlike normal adult tissues, presents an opportunity for targeted therapies.
- Targeting Nodal could help identify and treat aggressive melanoma cells.
- Further research into embryonic signaling pathways in cancer may yield novel diagnostic and therapeutic strategies.
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