Cited by 587Cancer Cells and MetastasisMechanisms of cancer metastasisDevelopmental Biology and Gene Regulation

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Mechanisms Governing Metastatic Dormancy and Reactivation

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Giancotti, Filippo G.·2013·Cell

DOI 10.1016/j.cell.2013.10.029PMC PMC4354734

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Abstract

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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Authors: Giancotti, F. G.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Giancotti, Filippo G.
ORCID: Giancotti, Filippo G.
Venue: Cell
Publisher: Elsevier BV
Published: 2013-11
Volume: 155
Issue: 4
Pages: 750-764
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.10.029
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
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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Mechanisms Governing Metastatic Dormancy and Reactivation

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