Mechanisms Governing Metastatic Dormancy and Reactivation
Open accessAbstract
Many cancer patients suffer from metastatic relapse several years after they have undergone radical surgery. Early cancer cell dissemination followed by a protracted period of dormancy potentially explains this prevalent clinical behavior. Increasing evidence suggests that the metastasis-initiating cells are cancer stem cells or revert to this functional state upon infiltrating a target organ. Their entry into dormancy and subsequent reactivation are governed by intrinsic programs and by contextual cues, which resemble those regulating the self-renewal capability of adult stem cells. In addition, metastatic cells undergoing reactivation are nursed by specialized extracellular matrix niches, which support positive signals, such as Wnt and Notch, and attenuate negative signals, such as BMP. In spite of significant remaining uncertainties, these findings provide a framework to understand the logic of metastatic dormancy and reactivation and open new avenues for therapeutic intervention.
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The in vivo senescence-like arrest may be unstable because dormant tumour cells can regrow after long periods.
“The analogy between senescence and dormancy in some tumours also implies that the in vivo senescence-like arrest may be unstable, because dormant tumour cells can regrow after long periods of time 130,140”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [140]
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- Authors
- Giancotti, F. G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Giancotti, Filippo G.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 155
- Issue
- 4
- Pages
- 750-764
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4354734
- OpenAlex
- W2088035579
- Cited by
- 586
- References
- 143
- Citations by year
- 2026: 20 · 2025: 35 · 2024: 45 · 2023: 68 · 2022: 47 · 2021: 50 · 2020: 53 · 2019: 47 · 2018: 53 · 2017: 39 · 2016: 57 · 2015: 44 · 2014: 28
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA175712)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- metastatic dormancy, cancer stem cells, metastasis-initiating cells, Wnt signaling, Notch signaling, BMP signaling, metastatic relapse, therapeutic interventions
- MeSH terms
- Animals, Extracellular Matrix, Humans, Neoplasm Metastasis, Neoplasms, Neoplastic Stem Cells
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