The dormant cancer cell life cycle

Phan, Tri Giang; Croucher, Peter I.

doi:10.1038/s41568-020-0263-0

Cited by 360 publications

(354 citation statements)

References 170 publications

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“…Although we are far from having a complete picture, pathways regulating dormancy are being better defined. A summary of known proteins and pathways studied in vitro and in vivo were shown in Tables 1 and 2 respectively, and the reader is referred to recent review articles about dormancy for further details (58,191,192).…”

Section: Mechanisms Of Cellular Dormancymentioning

confidence: 99%

Autophagy and Cancer Dormancy

et al. 2021

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Metastasis and relapse account for the great majority of cancer-related deaths. Most metastatic lesions are micro metastases that have the capacity to remain in a non-dividing state called “dormancy” for months or even years. Commonly used anticancer drugs generally target actively dividing cancer cells. Therefore, cancer cells that remain in a dormant state evade conventional therapies and contribute to cancer recurrence. Cellular and molecular mechanisms of cancer dormancy are not fully understood. Recent studies indicate that a major cellular stress response mechanism, autophagy, plays an important role in the adaptation, survival and reactivation of dormant cells. In this review article, we will summarize accumulating knowledge about cellular and molecular mechanisms of cancer dormancy, and discuss the role and importance of autophagy in this context.

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Section: Mechanisms Of Cellular Dormancymentioning

confidence: 99%

Autophagy and Cancer Dormancy

et al. 2021

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“…These effects of PTHrP are particularly important in the discussion of its role as a regulator of tumor dormancy as it has also been demonstrated that PTHrP lacking the NLS arrests cell cycle progression by increasing p27 Kip , a cyclin dependent kinase inhibitor, and decreasing phosphorylation of Rb (58,59). Cell cycle arrest in the G0-G1 phase is a key characteristic of quiescent cells (60,61) and p27 is elevated in G0 arrested cells (62,63). These findings in vascular smooth muscle cells are remarkable as they indicate that PTHrP can have paradoxical roles on mitogenesis depending on the mode of signaling: paracrine/autocrine vs. intracrine.…”

Section: Endocrine Autocrine and Paracrine Activity Of Pthrpmentioning

confidence: 99%

From Good to Bad: The Opposing Effects of PTHrP on Tumor Growth, Dormancy, and Metastasis Throughout Cancer Progression

Edwards

Johnson

2021

Front. Oncol.

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Parathyroid hormone related protein (PTHrP) is a multifaceted protein with several biologically active domains that regulate its many roles in normal physiology and human disease. PTHrP causes humoral hypercalcemia of malignancy (HHM) through its endocrine actions and tumor-induced bone destruction through its paracrine actions. PTHrP has more recently been investigated as a regulator of tumor dormancy owing to its roles in regulating tumor cell proliferation, apoptosis, and survival through autocrine/paracrine and intracrine signaling. Tumor expression of PTHrP in late stages of cancer progression has been shown to promote distant metastasis formation, especially in bone by promoting tumor-induced osteolysis and exit from dormancy. In contrast, PTHrP may protect against further tumor progression and improve patient survival in early disease stages. This review highlights current knowledge from preclinical and clinical studies examining the role of PTHrP in promoting tumor progression as well as skeletal and soft tissue metastasis, especially with regards to the protein as a regulator of tumor dormancy. The discussion will also provide perspectives on PTHrP as a prognostic factor and therapeutic target to inhibit tumor progression, prevent tumor recurrence, and improve patient survival.

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“…Metastatic recurrence is responsible for over 90% of cancer deaths and depends on the ability of tumor cells to migrate, seed other organs and restart to proliferate, often after an asymptomatic period named metastatic dormancy (6). During this period, pre-metastatic cells implement an array of strategies to ensure their survival and escape from immune surveillance (7). Among such strategies, adopting a nonproliferative state allows DCCs to persist for long time at metastatic sites, giving rise to tumor recurrence years or even decades after diagnosis.…”

Section: Inflammation Metastatic Reawakening and Cancer Recurrencementioning

confidence: 99%

COVID-19–Induced Modifications in the Tumor Microenvironment: Do They Affect Cancer Reawakening and Metastatic Relapse?

et al. 2020

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Severe coronavirus disease 2019 (COVID-19) causes an uncontrolled activation of the innate immune response, resulting in acute respiratory distress syndrome and systemic inflammation. The effects of COVID-19-induced inflammation on cancer cells and their microenvironment are yet to be elucidated. Here, we formulate the hypothesis that COVID-19-associated inflammation may generate a microenvironment favorable to tumor cell proliferation and particularly to the reawakening of dormant cancer cells (DCCs). DCCs often survive treatment of primary tumors and populate premetastatic niches in the lungs and other organs, retaining the potential for metastatic outgrowth. DCCs reawakening may be promoted by several events associated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including activation of neutrophils and monocytes/macrophages, lymphopenia and an uncontrolled production of pro-inflammatory cytokines. Among pro-inflammatory factors produced during COVID-19, neutrophil extracellular traps (NETs) released by activated neutrophils have been specifically shown to activate premetastatic cancer cells disseminated in the lungs, suggesting they may be involved in DCCs reawakening in COVID-19 patients. If confirmed by further studies, the links between COVID-19, DCCs reactivation and tumor relapse may support the use of specific anti-inflammatory and anti-metastatic therapies in patients with COVID-19 and an active or previous cancer.

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The dormant cancer cell life cycle

Cited by 360 publications

References 170 publications

Autophagy and Cancer Dormancy

Autophagy and Cancer Dormancy

From Good to Bad: The Opposing Effects of PTHrP on Tumor Growth, Dormancy, and Metastasis Throughout Cancer Progression

COVID-19–Induced Modifications in the Tumor Microenvironment: Do They Affect Cancer Reawakening and Metastatic Relapse?

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