Metastasis articles within Nature Communications

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  • Article
    | Open Access

    It is unclear if platelets regulate the growth of established metastases. Using syngeneic mouse models of metastasis, the authors show that platelets support the outgrowth of established metastases via immune suppression, and that targeting the platelet-specific receptor GPVI, efficiently reduces established metastases, providing a promising therapeutic avenue for inhibiting cancer metastasis.

    • Maria J. Garcia-Leon
    • , Cristina Liboni
    •  & Jacky G. Goetz

  • Article
    | Open Access

    An inflammatory-fibrotic tumor microenvironment supports metastatic disease progression in pancreatic ductal adenocarcinoma (PDAC). Here the authors show that metastasis-infiltrating macrophages influence metastasis-associated fibroblast (MAF) heterogeneity in liver metastatic PDAC, by promoting JAK/STAT signalling pathway activation in MAFs.

    • Meirion Raymant
    • , Yuliana Astuti
    •  & Michael C. Schmid

  • Article
    | Open Access

    Metastatic uveal melanoma is poorly responsive to immune checkpoint inhibition. Here, the authors analyse 100 uveal melanoma metastases using bulk and single cell RNA-seq, TCR analysis, and immune reactivity to show potent, yet, quiescent tumour infiltrating lymphocytes that can be harnessed by adoptive transfer to confer tumour immunity.

    • Shravan Leonard-Murali
    • , Chetana Bhaskarla
    •  & Udai S. Kammula

  • Article
    | Open Access

    Metastasis arises from disseminated tumour cells (DTCs) while the underlying mechanism of DTCs plasticity remains underexplored. Here, the authors show that spatially organized oncogenic enhancers on chromatin sustain the establishment of retinoic acid (RA)-stimulated transcriptional memory through activation of SOX9, supporting the escape of quiescent DTCs from NK-mediated immune surveillance.

    • Daniela Michelatti
    • , Sven Beyes
    •  & Alessio Zippo

  • Article
    | Open Access

    Detailed molecular studies are required to understand the differences between primary and metastatic upper tract urothelial carcinoma (UTUC). Here, the authors use genomics, transcriptomics and imaging mass cytometry to characterise the molecular profiles of primary and metastatic UTUC, and find that molecular subtypes remain highly conserved.

    • Kentaro Ohara
    • , André Figueiredo Rendeiro
    •  & Juan Miguel Mosquera

  • Article
    | Open Access

    MALAT1 is a long non-coding RNA that is known to suppress breast cancer lung metastasis. Here the authors show that MALAT1 is downregulated during osteoclastogenesis and its loss derepresses Tead3, promoting Nfatc1-mediated osteoclast differentiation and enhancing bone metastasis.

    • Yang Zhao
    • , Jingyuan Ning
    •  & Li Ma

  • Article
    | Open Access

    Studying survivorship and causes of death in patients with metastatic cancer remains an important task. Here, the authors characterise the causes of death in over a million patients with metastatic cancer, and predict the risk of death after diagnosis due to cancer-related or other causes.

    • Kyle Mani
    • , Daxuan Deng
    •  & Nicholas G. Zaorsky

  • Article
    | Open Access

    The molecular mechanisms underlying Double-Null Prostate Cancer (DNPC) pathogenesis remain elusive. Here, the authors show that co-activation of HGF/MET and Wnt/β-catenin signaling in mouse prostates results in DNPC-like tumor lesions with elevated expression of XPO1 and ribosomal proteins.

    • Won Kyung Kim
    • , Alyssa J. Buckley
    •  & Zijie Sun

  • Article
    | Open Access

    Aneuploidy is associated with cancer metastasis, but the causal relationship between them is unclear. Here the authors show that aneuploid murine embryonic stem cells lead to teratomas that can spread to multiple organs without requiring additional driver gene mutations and identify unique cell populations with high stemness in aneuploid teratomas.

    • Rong Xiao
    • , Deshu Xu
    •  & Yue Huang

  • Article
    | Open Access

    Understanding the mechanisms associated with cancer metastasis may help control cancer progression. Here the authors investigate the metabolism of metastasis initiating cells in breast cancer and show that their metastatic ability relies on fatty acid oxidation and the oxidative tricarboxylic acid cycle, which in turn regulates acetyl-CoA generation and the acetylation of histones on EMT related genes.

    • C. Megan Young
    • , Laurent Beziaud
    •  & Joerg Huelsken

  • Article
    | Open Access

    TGFbeta is known to promote cancer metastasis through the promotion of epithelial-mesenchymal transition (EMT). Here, the authors demonstrate that a TGFbeta induced circular RNA (circITGB6) promotes colorectal cancer metastasis via activation of the m6A reader protein, IGF2BP3, resulting in stabilization of an EMT-promoting gene, PDPN.

    • Ke Li
    • , Jiawei Guo
    •  & Yong Peng

  • Article
    | Open Access

    The suppressive immune microenvironment in colorectal cancer (CRC) liver metastasis remains to be explored. Here, the authors find tumor-associated macrophages in the liver microenvironment induces elevated secretion of FGL1 from cancer cells and hepatocytes which promotes CRC metastasis by suppressing the infiltration of T cells.

    • Jia-Jun Li
    • , Jin-Hong Wang
    •  & Huai-Qiang Ju

  • Article
    | Open Access

    The liver is the most common site of metastasis for pancreatic ductal adenocarcinoma (PDAC). Here, the authors demonstrate that β-glucan, a microbial component associated with trained immunity, activates liver-resident macrophages (Kupffer cells) and prevents PDAC metastasis to the liver

    • Stacy K. Thomas
    • , Max M. Wattenberg
    •  & Gregory L. Beatty

  • Article
    | Open Access

    Small cell lung cancers (SCLC) have often inactivating mutations in RB1. In this study, the authors demonstrate that RB1 loss mediates low expression of YAP1 in SCLC tumors ultimately promoting metastasis and they propose to use benzamide family HDAC inhibitors to induce YAP1 expression for prevention of metastases.

    • Zhengming Wu
    • , Junhui Su
    •  & Kun-Liang Guan

  • Article
    | Open Access

    Approaches to combine photodynamic therapy (PDT) with immunotherapy are emerging, allowing the treatment of primary and metastatic tumors. Here the authors report the design and characterization of a nanomaterial for theranostic imaging and photodynamic therapy eliciting anti-tumor immune response in preclinical cancer models.

    • Huiling Zhou
    • , Dongsheng Tang
    •  & Haihua Xiao

  • Article
    | Open Access

    The identification of factors that contribute to pre-metastatic niche can help prevent initial metastasis. Here the authors show that citrullinated fibrinogen complexes with serum amyloid A proteins (SAAs) to form a pre-metastatic niche in patients.

    • Yibing Han
    • , Takeshi Tomita
    •  & Sachie Hiratsuka

  • Article
    | Open Access

    The genomic landscape of brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC) remains to be explored. Here, the authors analyse a cohort of 233 patients with BM including 47 primary tumour, 42 extracranial metastatic matched samples and reveal distinct mutational patterns.

    • Anna Skakodub
    • , Henry Walch
    •  & Luke R. G. Pike

  • Article
    | Open Access

    3D scaffolds can be used to recapitulate key aspects of the microenvironment of primary tumors and metastatic organs. Here the authors use subcutaneous porous 3D scaffold implants as a tool to study the immune signals in the lungs of metastatic breast cancer, revealing multifaceted roles of neutrophils in regulating lung metastasis.

    • Jing Wang
    • , Ramon Ocadiz-Ruiz
    •  & Lonnie D. Shea

  • Article
    | Open Access

    The tumour-specific functions of SIX1 homeoprotein in Ewing sarcoma (ES) remain poorly understood. Here, the authors suggest that SIX1, which enhances metastasis in most tumour types, suppresses ES metastasis by co-regulating EWS/FLI1 target genes.

    • Connor J. Hughes
    • , Kaiah M. Fields
    •  & Heide L. Ford

  • Article
    | Open Access

    Distinguishing the drivers of metastasis versus those of the primary tumour in breast cancer remains challenging. Here, the authors explore primary-only, metastatic-only, and shared drivers in breast cancer using mammary-specific transposon mutagenesis screens, which leads to potential therapeutic targets to prevent metastasis.

    • Zhe Jiang
    • , YoungJun Ju
    •  & Eldad Zacksenhaus

  • Article
    | Open Access

    HER2 amplification in metastatic colorectal cancer (mCRC) identifies a group of patients with poorer prognosis. Here, the authors report the results of a phase II clinical trial assessing the clinical response and safety of trastuzumab deruxtecan as a third-line treatment in patients with mCRC with different HER2 expression levels

    • Takayuki Yoshino
    • , Maria Di Bartolomeo
    •  & Maria Di Bartolomeo

  • Article
    | Open Access

    Long-term metastatic relapse is observed in patients with luminal breast cancer (BC). Here, the authors show that fatty acid amide hydrolase is a tumour suppressor for lung metastasis in mouse models of BC and a predictor of metastasis in patients with luminal BC.

    • Isabel Tundidor
    • , Marta Seijo-Vila
    •  & Eduardo Pérez-Gómez

  • Article
    | Open Access

    The presence of peritoneal metastasis in pancreatic cancers is associated with poor prognosis. Here the authors show that hyaluronan and proteoglycan link protein-1 (HAPLN1) promotes tumour cell plasticity and pro-tumoral immune microenvironment to facilitate peritoneal dissemination in pancreatic cancers.

    • Lena Wiedmann
    • , Francesca De Angelis Rigotti
    •  & Juan Rodriguez-Vita

  • Article
    | Open Access

    The molecular mechanisms underlying lymph-node metastasis in head and neck squamous-cell carcinoma remain to be investigated. Here, the authors perform single-cell RNA sequencing of cancer cells and CD8 + T cells and suggest potential mechanisms of immune evasion during early metastasis.

    • Hong Sheng Quah
    • , Elaine Yiqun Cao
    •  & N. Gopalakrishna Iyer

  • Article
    | Open Access

    Implementing high-throughput single-cell DNA sequencing for the study of solid tumours has been challenging. Here, the authors present an optimised approach for snap-frozen tissue single nuclei extraction and DNA sequencing, which can be applied to study pancreatic ductal adenocarcinoma evolution and heterogeneity.

    • Haochen Zhang
    • , Elias-Ramzey Karnoub
    •  & Christine A. Iacobuzio-Donahue

  • Article
    | Open Access

    It is critical to understand the factors that are associated with nasopharyngeal carcinoma (NPC) progression, metastasis and response to therapy. Here, the authors analyse primary and metastatic NPC samples using bulk and single-cell sequencing, and find two distinct evolutionary routes that lead to metastasis.

    • Mei Lin
    • , Xiao-Long Zhang
    •  & Ming-Yuan Chen

  • Article
    | Open Access

    Understanding the heterogeneity of growth, response to therapy and progression dynamics in metastatic colorectal cancer (mCRC) remains critical. Here, the authors analyse lesion-specific response heterogeneity in 4,308 mCRC patients and find that organ-level progression sequence is associated with long-term survival.

    • Jiawei Zhou
    • , Amber Cipriani
    •  & Yanguang Cao

  • Article
    | Open Access

    Enhancer of zeste homolog 2 (EZH2) has been associated with poor prognosis in triple negative breast cancer (TNBC). Here, the authors suggest a potential role for trimethylation function of EZH2 in driving peritoneal metastasis in TNBC.

    • Ayushi Verma
    • , Akhilesh Singh
    •  & Dipak Datta

  • Article
    | Open Access

    Melanoma brain metastases (MBM) show heterogeneous therapeutic response determined by incompletely understood mechanisms. Here, the authors use a multi-OMICS approach and targeted sequencing (TargetSeq) to decipher programs that may define molecular subsets of MBM and their response to therapy.

    • Josefine Radke
    • , Elisa Schumann
    •  & Torben Redmer

  • Article
    | Open Access

    The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures.

    • Ariane F. Busso-Lopes
    • , Leandro X. Neves
    •  & Adriana F. Paes Leme

  • Article
    | Open Access

    The Bladder Cancer Advocacy Network established the UC-GENOME study in order to create a biobank and data repository for metastatic urothelial carcinoma. Here, the authors present the first characterization and analysis of DNA and RNA sequencing data from the 218 patients included in the UC-GENOME.

    • Jeffrey S. Damrauer
    • , Wolfgang Beckabir
    •  & Matthew I. Milowsky

  • Article
    | Open Access

    ESRP1 is reported to regulate the alternative splicing of some genes involved in epithelial–mesenchymal transition. Here the authors show that LRRFIP2 is a target of ESRP1 and that two spliced variants of LRRFIP2 have opposing functions in gastric cancer metastasis

    • Jihee Lee
    • , Kyoungwha Pang
    •  & Seong-Jin Kim

  • Article
    | Open Access

    Cancer cells and macrophages can infiltrate and remodel the extracellular matrix (ECM). Here, by using native basement membrane-interstitial matrix explants as model and live cell confocal imaging, the authors reveal divergent mechanisms used by cancer cells and macrophages to penetrate native basement membrane barriers.

    • Julian C. Bahr
    • , Xiao-Yan Li
    •  & Stephen J. Weiss

  • Article
    | Open Access

    Methylmalonic acid (MMA) is increased in aging as well as produced by advanced tumors, and can drive pro-aggressive changes in these tumor cells. Here, the authors show that MMA can also act on fibroblasts in the tumor microenvironment, recruiting and activating them to further support tumor progression.

    • Zhongchi Li
    • , Vivien Low
    •  & John Blenis

  • Article
    | Open Access

    Cell migration regulates diverse (patho)physiological processes, including cancer metastasis. Here the authors show that the chloride ion channel SWELL1 and the ion exchanger NHE1 are preferentially enriched at the trailing and leading edges, respectively, of migrating cells and regulate cell volume to propel confined cells, favouring breast cancer cell extravasation and metastasis.

    • Yuqi Zhang
    • , Yizeng Li
    •  & Konstantinos Konstantopoulos

  • Article
    | Open Access

    Brain metastases (BrMs) in non-small cell lung cancer (NSCLC) are associated with dismal outcomes, and are possibly sustained by the brain microenvironment. Here, the authors analyse NSCLC BrMs using Digital Spatial Profiling and reveal fibrosis, immune suppression, and cell reprogramming in the BrM microenvironment.

    • Qi Zhang
    • , Rober Abdo
    •  & Shawn Shun-Cheng Li

  • Article
    | Open Access

    Accumulating evidence suggest that chemotherapy could paradoxically promote cancer metastasis. Here the authors report that, in preclinical breast cancer models, adjuvant treatment with doxorubicin induces the formation of an immunosuppressive metastatic niche that promotes relapse but that can be reverted with pharmacological blockade of complement signaling.

    • Lea Monteran
    • , Nour Ershaid
    •  & Neta Erez

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