Article
|
Open Access
Featured
-
-
Article
| Open AccessAcetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer
The therapies for bone metastatic prostate cancer are limited and the underlying mechanisms are unclear. Here, the authors show that bone derived TGF-β induces acetylation of KLF5 (Ac-KLF5), and Ac-KLF5 promotes prostate cancer bone metastasis and resistance to docetaxel by upregulating CXCR4.
- Baotong Zhang
- , Yixiang Li
- & Jin-Tang Dong
-
Article
| Open AccessPredicting gastric cancer outcome from resected lymph node histopathology images using deep learning
The ratio of tumour area to metastatic lymph node area (T/MLN) is a clinical indicator that can improve prognosis prediction of gastric cancer. Here, the authors use machine learning on whole slide images to generate a method that can predict metastatic lymph nodes and obtain T/MLN.
- Xiaodong Wang
- , Ying Chen
- & Guanzhen Yu
-
Article
| Open AccessAn ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism
The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch.
- Marisa Nacke
- , Emma Sandilands
- & David M. Bryant
-
Article
| Open AccessInter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling
The inter- and intra-tumor heterogeneity of metastatic prostate cancer (mPC) is underexplored. Here the authors use Digital Spatial Profiling to study gene and protein expression heterogeneity in 27 mPC patients, finding variation in associated pathways and potential immunotherapy targets.
- Lauren Brady
- , Michelle Kriner
- & Peter S. Nelson
-
Article
| Open AccessCD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
Dormancy of disseminated cancer cells has been described in patients with breast cancer and associated with late metastatic relapses. Here the authors show that CD39+PD-1+CD8+ T cells correlate with increased disease free survival post-resection in breast cancer patients, and promote dormancy in a preclinical model.
- Paulino Tallón de Lara
- , Héctor Castañón
- & Maries van den Broek
-
Article
| Open AccessMesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer
The effects of bone-marrow derived MSCs on prostate cancer cells remain unknown. Here the authors show that MSC-derived IL-28 induces prostate cancer cell apoptosis via IL-28Rα-STAT1 signalling, while acquired resistance to apoptosis is associated with a shift in IL-28Rα signalling via STAT1 to STAT3.
- Jeremy J. McGuire
- , Jeremy S. Frieling
- & Conor C. Lynch
-
Article
| Open AccessWhole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features
Molecular landscapes of metastatic colorectal cancers (mCRC) have often been restricted to coding regions or low numbers of patients. Here the authors present a whole-genome landscape of 429 mCRC patients, revealing the mutational impact of prior therapies and potential actionable targets.
- Pauline A. J. Mendelaar
- , Marcel Smid
- & Saskia M. Wilting
-
Article
| Open AccessNicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung
Smoking is known to impact tumor immunity and promote tumor progression. Here, the authors show that chronic nicotine exposure promotes the lung pre-metastatic niche formation by recruiting pro-tumor N2-neutrophils that release lipocalin-2.
- Abhishek Tyagi
- , Sambad Sharma
- & Kounosuke Watabe
-
Article
| Open AccessHIF1A signaling selectively supports proliferation of breast cancer in the brain
The mechanisms underlying the growth of breast cancer metastasis in the brain are unclear. Here, the authors use an intracranial injection mouse model and single-cell analysis of patient circulating tumour cells to demonstrate that increased hypoxic and HIF1A signalling promotes tumour growth in the brain.
- Richard Y. Ebright
- , Marcus A. Zachariah
- & Shyamala Maheswaran
-
Article
| Open AccessST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL
Understanding the molecular events controlling melanoma progression are necessary to find improved therapeutics. Here, the authors report oncogenic SOX2-GLI1 transcriptional complex to drive melanoma invasion through the induction of the sialyltransferase ST3GAL1, and report ST3GAL1-AXL axis as driver of melanoma metastasis.
- Silvia Pietrobono
- , Giulia Anichini
- & Barbara Stecca
-
Article
| Open AccessTransient commensal clonal interactions can drive tumor metastasis
Cooperative interactions among tumor cells may have important implications for metastasis. Here, the authors examined the spatio-temporal nature of interactions among clonal populations of ovarian carcinoma cells and found that transient interactions cells can promote metastases via commensal interactions.
- Suha Naffar-Abu Amara
- , Hendrik J. Kuiken
- & Joan S. Brugge
-
Article
| Open AccessKetohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer
Apart from the enzymatic role of ketohexokinase isoform A (KHK-A) in fructose metabolism the alternative physiological functions of the enzyme are unclear. Here, the authors show that KHK-A mediates fructose-induced metastasis in breast cancer through a nuclear role in repressing the transcriptional activity of the cell-adhesion molecule CDH1.
- Jiyoung Kim
- , Jengmin Kang
- & Jong-Wan Park
-
Article
| Open AccessPan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation
Mutations in TP53 and hyperactivation of the PI3K/AKT pathway are the two most frequent drivers of cancer progression across multiple human tumour types. Here, the authors identify two TAp63 regulated long non-coding RNAs, TROLL-2 and TROLL-3, that connect these oncogenic pathways, thus promoting tumour and metastasis formation in a wide variety of cancer types.
- Marco Napoli
- , Xiaobo Li
- & Elsa R. Flores
-
Article
| Open AccessAKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent Vimentin degradation
The role of long non-coding RNA (lncRNA) in AKT-driven tumor development is unclear. Here, the authors identify VAL (Vimentin associated lncRNA) to be directly induced by AKT/STAT3 signaling and report a lncRNA-mediated mechanism for active AKT-driven EMT-independent lung adenocarcinoma metastasis.
- Han Tian
- , Rong Lian
- & Junchao Cai
-
Article
| Open AccessProstate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy
The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. Here, the authors use deep genomic sequencing and histopathological information to trace tumor evolution both within the prostate and during metastasis in ten men.
- D. J. Woodcock
- , E. Riabchenko
- & D. C. Wedge
-
Article
| Open AccessDual roles of neutrophils in metastatic colonization are governed by the host NK cell status
The role of neutrophils in the regulation of tumour growth and metastasis remains controversial. Here, the authors demonstrate that neutrophils, by exerting inhibitory effects on cytotoxic NK cells, show a net pro-metastatic effect in immune-competent mice, while they are tumoricidal and anti-metastatic in NK cell-deficient hosts.
- Peishan Li
- , Ming Lu
- & Guangwen Ren
-
Article
| Open AccessMulti-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases
Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.
- Roy Rabbie
- , Naser Ansari-Pour
- & David J. Adams
-
Article
| Open AccessITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells
The integrin ITGB3 has been described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. Here the authors describe thus far unknown roles of ITGB3 in the uptake of extracellular vesicles, required for colony growth of breast cancer cells.
- Pedro Fuentes
- , Marta Sesé
- & Santiago Ramón y Cajal
-
Article
| Open AccessPancreatic cancers suppress negative feedback of glucose transport to reprogram chromatin for metastasis
Distant metastases from pancreatic cancer patients were previously reported by the authors to be dependent on the glucose-metabolizing enzyme phosphogluconate dehydrogenase (PGD). Here the authors report a novel metabolic adaptation that that stably activates PGD to reprogram metastatic chromatin.
- Matthew E. Bechard
- , Rana Smalling
- & Oliver G. McDonald
-
Article
| Open AccessMutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
p53 mutants can promote tumorigenesis by affecting fundamental cellular pathways and functions. In this study, the authors demonstrate a novel mutant-p53/HIF1α/miR-30d axis that impacts Golgi structure, trafficking, and secretion of proteins essential for tumor growth and metastasis.
- Valeria Capaci
- , Lorenzo Bascetta
- & Giannino Del Sal
-
Article
| Open AccessPancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target
Metastatic dissemination contributes to the lethality in pancreatic ductal adenocarcinoma (PDAC). Here, the authors perform RNA-sequencing on patient derived circulating tumor cells (CTCs) and identify three major CTC subgroups, and show the therapeutic potential of targeting LIN28B/let-7 pathway to halt cancer metastasis.
- Joseph W. Franses
- , Julia Philipp
- & David T. Ting
-
Article
| Open AccessRab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth
Mechanisms governing adaptation of breast cancer to the brain metastatic microenvironment are unclear. Here, the authors use RNA-sequencing and Drosophila screening to identify Rab11b-mediated endosomal recycling as a unique mechanism for adaptation to a challenging metastatic microenvironment, which can be exploited by repurposing statins.
- Erin N. Howe
- , Miranda D. Burnette
- & Siyuan Zhang
-
Article
| Open AccessContext specificity of the EMT transcriptional response
It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16 kinase inhibitor screens, and find that EMT transcriptional responses are context specific and EMT is not a single, linear transition.
- David P. Cook
- & Barbara C. Vanderhyden
-
Article
| Open AccessProteogenomics analysis unveils a TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas
Papillary thyroid cancer (PTC) is one of the most common type of endocrine malignancy. Here, the authors use proteogenomic approaches to analyse the primary tumour and lymph node metastases from a PTC patient and report an oncogenic RET fusion, and potential druggable targets from the ubiquitin signaling machinery for treating human PTCs.
- Aswini Krishnan
- , Jean Berthelet
- & Krishnaraj Rajalingam
-
Article
| Open AccessMapping the spreading routes of lymphatic metastases in human colorectal cancer
Lymphatic metastases are closely associated with tumor relapse and reduced survival in colorectal cancer (CRC). Here, the authors analysed the primary tumours, lymph node metastasis and liver metastasis of ten CRC patients and reveal co-existence of diverse modes of metastasis in the same patient.
- Chong Zhang
- , Lin Zhang
- & Haizeng Zhang
-
Article
| Open AccessMolecular profiling of driver events in metastatic uveal melanoma
The genetics of uveal melanoma has mainly been studied in primary tumours. In this study, the authors perform whole genome sequencing as well as immune cell profiling of biopsy samples obtained from metastatic uveal melanoma patients, providing an updated genomic landscape of these advanced lesions.
- Joakim Karlsson
- , Lisa M. Nilsson
- & Jonas A. Nilsson
-
Article
| Open AccessLoss of testosterone impairs anti-tumor neutrophil function
It is known that there are sex differences in the incidence and prognosis of certain cancers, including melanoma. In this study, the authors utilize a melanoma model to reveal that castrated mice have a higher metastatic burden associated with androgen dependent impaired neutrophil function.
- Janet L. Markman
- , Rebecca A. Porritt
- & Moshe Arditi
-
Article
| Open AccessDifferential regulation of breast cancer bone metastasis by PARP1 and PARP2
The effect of PARP inhibitors on bone mass and bone metastasis are unclear. Here, the authors show that PARP1/2 dual inhibitors may increase cancer bone metastasis through PARP2-dependent regulation of immature myeloid cells, and cause bone loss through PARP1/2-dependent regulation of osteoclasts.
- Hao Zuo
- , Dengbao Yang
- & Yihong Wan
-
Article
| Open AccessSubpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion
The presence of phenotypic heterogeneity in collectively invading cells suggests cooperation amongst distinct subtypes of cells to promote invasion and metastasis. Here, the authors use chemical biology tools and report metabolic heterogeneity within the lung cancer collective invasion pack.
- R. Commander
- , C. Wei
- & A. I. Marcus
-
Article
| Open AccessTargeting the CK1α/CBX4 axis for metastasis in osteosarcoma
Osteosarcoma is an aggressive tumour and little is known the mechanisms underpinning its highly metastatic nature. Here, the authors highlight a role for the CK1α/CBX4 axis in driving metastasis, suggesting that this pathway might be targeted for therapeutic benefit.
- Xin Wang
- , Ge Qin
- & Tiebang Kang
-
Article
| Open AccessDistinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models
The effects of anesthetics on cancer metastasis are largely unknown. Here, the authors show in two preclinical mouse models that surgical resection of primary tumours under anesthesia with sevoflurane leads to more lung metastases than with propofol and that such distinct effects are associated with change of cytokines and modulation of myeloid cells in the lung.
- Ru Li
- , Yujie Huang
- & Jun Lin
-
Article
| Open AccessChromosome arm aneuploidies shape tumour evolution and drug response
Chromosome arm-level aneuploidies (CAAs) are frequently observed in cancer. Here, the authors analyse CAA landscapes across different tumour types, relating these chromosome arm gains and losses to tumour evolution, metastasis, patient survival and response to a range of anti-cancer therapies.
- Ankit Shukla
- , Thu H. M. Nguyen
- & Pascal H. G. Duijf
-
Article
| Open AccessMelanoblast transcriptome analysis reveals pathways promoting melanoma metastasis
Metastatic cells can mimic many of the phenotypic behaviors of embryonic cells. Here, the authors generate a melanoblast-specific transcriptome using a genetically engineered mouse model and identify KDELR3 as a pro-metastasis gene in melanoma.
- Kerrie L. Marie
- , Antonella Sassano
- & Pravin J. Mishra
-
Article
| Open AccessSexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases
It is known that estrogens can affect the immune response to cancer. Here, the authors show that estrogen depletion through ovariectomy reduces the extent of liver metastasis and that this is accompanied by a decrease in the number and function of immunosuppressive cells in the metastatic microenvironment.
- Simon Milette
- , Masakazu Hashimoto
- & Pnina Brodt
-
Article
| Open AccessPSPC1-interchanged interactions with PTK6 and β-catenin synergize oncogenic subcellular translocations and tumor progression
PSPC1 has a critical role in promoting EMT and metastasis. Here, the authors demonstrate that PSPC1 is the contextual determinant of the oncogenic switch of PTK6/β-catenin subcellular localizations to drive metastasis of hepatocellular carcinoma cells via a PSPC1/PTK6/β-catenin signaling.
- Yaw-Dong Lang
- , Hsin-Yi Chen
- & Yuh-Shan Jou
-
Article
| Open AccessZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer
Non-small cell lung cancer (NSCLC) is often associated with metastasis to the lungs. Here, the authors perform independent screens and identify NuRD as a co-repressor of ZEB1, and demonstrate TBC1D2b as a downstream target of ZEB1/NuRD complex regulating NSCLC metastasis.
- Roxsan Manshouri
- , Etienne Coyaud
- & Don L. Gibbons
-
Article
| Open AccessAn inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases
Successful anticancer immunotherapy should induce robust systemic immunity against metastases. Here, the authors engineer an inhalable nano-STING agonist, which synergizes with fractionated radiation to control lung metastases and confers long-term systemic antitumor immunity in mice.
- Yang Liu
- , William N. Crowe
- & Dawen Zhao
-
Article
| Open AccessEGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming
Triple-negative breast cancer is an aggressive form of the disease. Here, the authors identify EGFL9 as a mediator of metastasis in TNBC through interactions with cMET.
- Fanyan Meng
- , Ling Wu
- & Guojun Wu
-
Article
| Open AccessMicroenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
In breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation
- Rachel Eyre
- , Denis G. Alférez
- & Robert B. Clarke
-
Article
| Open AccessN6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis
Liver metastasis of colorectal cancer leads to poor prognosis. Here the authors report that an N6-methyladenosine modified circular RNA is upregulated in colorectal cancer and promotes liver metastasis by enhancing the stability of HMGA2 mRNA.
- Ri-Xin Chen
- , Xin Chen
- & Dan Xie
-
Article
| Open AccessThe CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis
Breast cancer cells often invade the bone tissue and remain dormant until they are induced to colonize the metastatic site. Here the authors develop an ex vivo co-culture system consisting of bone and cancer cells from mice and show that CXCL5 has a role in metastatic colonization in the bone.
- Ricardo Romero-Moreno
- , Kimberly J. Curtis
- & Laurie E. Littlepage
-
Article
| Open AccessHistone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes
The prognosis of cancer patients with lymph node (LN) metastasis is worse than those without. Here, the authors report that while histone deacetylase 11 (HDAC11) inhibition suppresses tumor growth within the LN, it also promotes cancer cell migration out of the LN to form distant metastasis, and therefore suggest caution with HDAC inhibitors.
- Patrick L. Leslie
- , Yvonne L. Chao
- & Chad V. Pecot
-
Article
| Open AccessAutophagy inhibition elicits emergence from metastatic dormancy by inducing and stabilizing Pfkfb3 expression
Cancer cells can use autophagy as a mechanism of surviving from external stresses. Here, the authors show that Pfkfb3, a glycolytic gene, is expressed in metastatic breast cancer cells but not in dormant cells that demonstrate features of autophagy.
- Alyssa La Belle Flynn
- , Benjamin C. Calhoun
- & William P. Schiemann
-
Article
| Open AccessRelaxin gene delivery mitigates liver metastasis and synergizes with check point therapy
Activated hepatic stellate cells are associated with fibrosis and liver metastases. Here, the authors identify an endogenous role of relaxin in regulating the activation of hepatic stellate cells and report nanoparticle-mediated relaxin gene therapy to mitigate fibrosis and liver metastasis.
- Mengying Hu
- , Ying Wang
- & Leaf Huang
-
Article
| Open AccessMetabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation
Cancer cells must develop distinct metabolic adaptations to survive in challenging metastatic environments. Here, the authors find, via an in vivo RNAi screen, that the aldo-keto reductase AKR1B10 limits the toxic side effects of oxidative stress to sustain fatty acid oxidation and promote metastatic colonisation.
- Antoinette van Weverwijk
- , Nikolaos Koundouros
- & Clare M. Isacke
-
Article
| Open AccessRan promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion
Ran, a nucleus-cytoplasm shuttle protein, is implicated in cancer development and survival. Here, the authors show that Ran binds RhoA to impair its degradation and allow its localisation to the plasma membrane of ovarian cancer cells for tumour invasion.
- Kossay Zaoui
- , Zied Boudhraa
- & Anne-Marie Mes-Masson
-
Article
| Open AccessCHML promotes liver cancer metastasis by facilitating Rab14 recycle
Metastasis-associated recurrence is a major cause of poor prognosis in hepatocellular carcinoma. Here, the authors show that expression of choroideremia-like (CHML) is elevated and associates with poor prognosis in hepatocellular carcinoma, and mechanistically CHML promotes metastasis in a Rab14-dependent manner.
- Tian-Wei Chen
- , Fen-Fen Yin
- & Dong Xie
-
Article
| Open AccessSialyl Lewisx-P-selectin cascade mediates tumor–mesothelial adhesion in ascitic fluid shear flow
Tumor cell in the peritoneum are often exposed to shear forces generated by ascitic flow during metastasis. Here, the authors show that metastatic cancer stem cells tether more and roll slower than the non-metastatic counterparts, and that sialyl-Lewisx -P-selectin axis mediates peritoneal metastasis.
- Shan-Shan Li
- , Carman K. M. Ip
- & Alice S. T. Wong
-
Article
| Open AccessCollective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
Modelling and visualizing tumor metastasis in Drosophila has been a challenge. Here, the authors show that constitutive expression of Sna in primary adult Drosophila intestinal tumors drives EMT and dissemination of tumor cells, induces collective cell migration and formation of polyclonal metastases.
- Kyra Campbell
- , Fabrizio Rossi
- & Andreu Casali