ArticleNature2015
The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 286 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
286 citing papers in PubMed, 1 synthesis or guideline pooled it, 469 citations in OpenAlex.
- Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-Analysis.Frontiers in nutrition · 2022Pooled it
- A feedback mechanism between E3 ligase RNF122 and HIF-1α inhibits aggressive behavior in breast cancer.Oncogene · 2026Article
- Microenvironment plays a critical role in modulating tumor cell dormancy: Current perspectives and potential treatment options.World journal of clinical oncology · 2026Review
- Dual-Emission Fluorescent Probe for Simultaneous Visualization of Monoamine Oxidase A and Lysyl Oxidase in Alzheimer's Disease Cell Models.Chemical & biomedical imaging · 2026Article
- LOX From Salivary Adenoid Cystic Carcinoma-Associated Fibroblast Promotes Fibrosis in the Pulmonary Pre-metastatic Niche.International dental journal · 2026Article
- Nanomedicine-Based Strategies Targeting Macrophage Polarization in Breast Cancer Bone Metastasis: An Updated Review.Breast cancer (Dove Medical Press) · 2026Review
- Review of the premetastatic niche in liver cancer bone metastases.International journal of clinical and experimental pathology · 2026Review
- 3D Morphometry of Preclinical Bone Disease Models Beyond Osteoporosis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Immune Microenvironment in Breast Cancer Metastasis.Advances in experimental medicine and biology · 2025Review
- Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment.Current medicinal chemistry · 2025Review
- Pulmonary lysyl oxidase expression and its role in seeding Lewis lung carcinoma cells.Clinical & experimental metastasis · 2024Article
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- Differential bone morphology and hypoxia activity in skeletal metastases of ERCommunications biology · 2024Article
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- Biological characterization of breast cancer spheroid formed by fast fabrication method.In vitro models · 2024Article
- Molecular mechanism of bone metastasis in breast cancer.Frontiers in oncology · 2024Review
- Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.Journal of Cancer · 2024Review
- Lysyl Oxidase (LOX) Family Proteins: Key Players in Breast Cancer Occurrence and Progression.Journal of Cancer · 2024Review
- The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer.Frontiers in pharmacology · 2024Review
- Mechanisms of Organ-Specific Metastasis of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
226 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2023-04-17Unreliable Data · Unreliable Image ·
- Commented on by
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- Retracted
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis, independent of RANK ligand, which disrupts normal bone homeostasis leading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications.
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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.