Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins
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Updated: Jul 11, 2026
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Jennifer M Bailey1, Pankaj K Singh, Michael A Hollingsworth
1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Abstract:
This review will highlight the significance of three critical pathways in developmental biology and our emerging understanding of their roles in regulating tumor metastasis: Bone morphogenic protein (BMP), Notch and Sonic hedgehog (SHH). We will discuss parallels between their known roles in development and how these processes can be used by tumor cells to create microenvironments that enhance tumor metastasis. That tumor cells usurp pathways critical to the developing embryo is not surprising, as many of the normal developmental programs include processes that are also seen during tumor progression to a metastatic phenotype, including epithelial to mesenchymal transition (EMT), tissue specific morphogenesis, cellular motility and invasion. BMPs are involved in EMT, contribute to tissue specific morphogenesis, and are expressed in highly-metastatic tumor cells. BMPs have also been hypothesized to have a role in the establishment of a pre-neoplastic niche. Notch and SHH facilitate neovascularization, angiogenesis, EMT and can contribute to the maintenance of highly-metastatic tumor stem cells.
Insights
Tumor cells hijack developmental pathways like Bone morphogenic protein (BMP), Notch, and Sonic hedgehog (SHH) to promote metastasis. Understanding these pathways offers new insights into cancer progression and potential therapeutic targets.
Area of Science:
- Developmental Biology
- Cancer Biology
- Molecular Oncology
Background:
- Developmental pathways are crucial for embryonic development.
- Tumor metastasis involves processes similar to embryonic development, such as epithelial to mesenchymal transition (EMT).
- Specific developmental pathways are increasingly recognized for their roles in cancer progression.
Purpose of the Study:
- To review the roles of Bone morphogenic protein (BMP), Notch, and Sonic hedgehog (SHH) pathways in tumor metastasis.
- To highlight parallels between developmental functions and their subversion by cancer cells.
- To discuss how these pathways create microenvironments that enhance metastasis.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of the roles of BMP, Notch, and SHH in both development and cancer metastasis.
- Discussion of mechanisms including EMT, morphogenesis, and stem cell maintenance.
Main Results:
- BMP signaling is implicated in EMT, morphogenesis, and the pre-neoplastic niche.
- Notch and SHH signaling pathways contribute to neovascularization, angiogenesis, EMT, and cancer stem cell maintenance.
- Tumor cells exploit these developmental pathways to facilitate metastatic spread.
Conclusions:
- The BMP, Notch, and SHH pathways are critical regulators of tumor metastasis.
- Understanding the subversion of developmental programs by cancer cells is key to developing anti-metastatic therapies.
- Targeting these hijacked pathways holds promise for novel cancer treatments.
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