ArticleOncotarget2016
Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Phytohormone Signaling Induces Dormancy and Apoptosis in Prostate Cancer Disseminated Tumor Cells.Medical research archives · 2026Article
- Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025Review
- Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Abscisic acid signaling through LANCL2 and PPARγ induces activation of p38MAPK resulting in dormancy of prostate cancer metastatic cells.Oncology reports · 2024Article
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- Apoptotic cell clearance components in inflammatory arthritis.Immunological reviews · 2023Review
- Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution.Cancer metastasis reviews · 2023Review
- Slow-cycling (dormant) cancer cells in therapy resistance, cancer relapse and metastasis.Seminars in cancer biology · 2022Review
- Interaction between prostate cancer stem cells and bone microenvironment regulates prostate cancer bone metastasis and treatment resistance.Journal of Cancer · 2022Review
- Targeting MERTK and AXL inCancers · 2021Review
- The pathogenesis of bone metastasis in solid tumors: a review.Croatian medical journal · 2021Review
- MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- The current paradigm and challenges ahead for the dormancy of disseminated tumor cells.Nature cancer · 2020Review
- Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer.The Journal of experimental medicine · 2020Article
- Bone microenvironment signaling of cancer stem cells as a therapeutic target in metastatic prostate cancer.Cell biology and toxicology · 2020Review
- Wnt5a induces and maintains prostate cancer cells dormancy in bone.The Journal of experimental medicine · 2019Article
- Minimal residual disease in prostate cancer patients after primary treatment: theoretical considerations, evidence and possible use in clinical management.Biological research · 2018Review
- Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.Cancers · 2018Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledGAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment.We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c.
settingInterestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo.Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.