Featured
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| 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
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Article
| Open AccessEvaluating cell lines as models for metastatic breast cancer through integrative analysis of genomic data
While cell lines and organoids are extensively used to study cancer, how closely they resemble the disease in patients remains unclear. Here, Liu et al. shed light on this issue by comparing the genomic and transcriptomic profiles of different breast cancer cell lines and organoids to data from patient-derived breast cancer metastases.
- Ke Liu
- , Patrick A. Newbury
- & Bin Chen
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Article
| Open AccessHydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells
Transcriptome analysis of circulating tumor cells (CTCs) provides insights into monitoring target therapeutics and underlying tumor metastasis. Here the authors present Hydro-Seq, a contamination-free high-throughput hydrodynamic scRNA-seq barcoding technique for rare CTCs.
- Yu-Heng Cheng
- , Yu-Chih Chen
- & Euisik Yoon
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Article
| Open AccessCollagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung
Collagen is a dynamic component of both the tumor and metastatic niche. Here, the authors show that airway smooth muscle cells are a collagen III rich niche bladder cancer cells expressing CD167a, and Stat3 is a downstream target for abrogating these collagen III/CD167a-driven metastatic foci.
- Yu-Cheng Lee
- , Antonina V. Kurtova
- & Keith Syson Chan
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Article
| Open AccessRETRACTED ARTICLE: RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
RNA m6A methylation is known to be dysregulated in many cancers. Here, the authors show that m6A methylation of Snail mRNA regulates its translation with potential effects on epithelial mesenchymal transition.
- Xinyao Lin
- , Guoshi Chai
- & Hongsheng Wang
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Article
| Open AccessPrimary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model
Dissemination of tumor cells from the primary site is an early event. Here, the authors show that the early disseminated tumor cells are actively cleared by the host cytotoxic T lymphocytes induced by the primary tumor and that infiltration of granulocytic myeloid-derived suppressor cells counteracts such immune protection and allow metastasis development.
- Raziye Piranlioglu
- , EunMi Lee
- & Hasan Korkaya
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Article
| Open AccessImmune modulation of liver sinusoidal endothelial cells by melittin nanoparticles suppresses liver metastasis
Liver sinusoidal endothelial cells are known to promote immune tolerance in liver. Here, the authors target these cells using melittin nanoparticles and show alterations in the liver immune environment and suppression of liver metastases.
- Xiang Yu
- , Lu Chen
- & Zhihong Zhang
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Article
| Open AccessRETRACTED ARTICLE: Mir20a/106a-WTX axis regulates RhoGDIa/CDC42 signaling and colon cancer progression
Wilms tumor gene on the X chromosome (WTX) is commonly downregulated in human cancers. Here the authors show that in colorectal cancer (CRC) WTX expression is downregulated via miR20a and miR160a and its loss promotes tumor development and liver metastasis by disrupting the interaction between RhoGDIα and CDC42 leading to the activation of the CDC42 downstream cascades.
- Gui-fang Zhu
- , Yang-wei Xu
- & Qing-ling Zhang
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Article
| Open AccessCancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis
The mechanisms underlying pre-metastatic niche formation by cancer derived exosomes is unclear. Here they show that colorectal cancer (CRC) derived exosomal miR-25-3p promotes vascular leakiness and angiogenesis, CRC metastasis, and is upregulated in CRC pateints with metastasis, and suggest miR-25-3p as a biomarker for CRC metastasis.
- Zhicheng Zeng
- , Yuling Li
- & Li Liang
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Article
| Open AccessNSD2 is a conserved driver of metastatic prostate cancer progression
Identifying cell intrinsic mechanisms promoting metastasis are necessary to develop new cancer therapeutics. Here they do cross-species computational analysis and identify nuclear receptor binding SET domain Protein 2 (NSD2) as a driver of prostate cancer metastasis.
- Alvaro Aytes
- , Arianna Giacobbe
- & Cory Abate-Shen
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Article
| Open AccessPlasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis
Neutrophil extracellular traps (NETs) are known to promote metastasis in mouse models. Here the authors show plasma redox imbalance caused by albumin oxidation to induce inflammation-independent NETosis and lung metastasis, and albumin oxidation and reduced plasma free thiol to be associated with lung metastasis in a cohort of head and neck cancer patients.
- Minoru Inoue
- , Ryota Nakashima
- & Scott V. Bratman
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Article
| Open AccessHigh-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer
It is unclear how intra-tumoral heterogeneity contributes to metastasis. Here the authors study the clonal dynamics of triple negative breast cancer metastasis using patient derived xenografts and demonstrate that primary tumor clones harbor properties that support seeding and colonization of multiple organs.
- Gloria V. Echeverria
- , Emily Powell
- & Helen Piwnica-Worms
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Article
| Open AccessA biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis
Photodynamic therapy is usually ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Here, the authors design a biomimetic nanoreactor which can convert nutriment glucose into toxic singlet oxygen via chemiluminescence resonance energy transfer with no light excitation and demonstrate its high efficacy in a mouse lung metastatic model.
- Zhengze Yu
- , Ping Zhou
- & Bo Tang
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Article
| Open AccessHysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability
The epithelial-mesenchymal transition (EMT) is a dynamic process that plays important roles in cancer progression and metastasis. Here, the authors characterize a non-linear hysteretic response of E-cadherin repression during TGFβ-induced EMT that is controlled by the strength of the miR-200s/ZEBs negative feedback loop and enhances metastasis.
- Toni Celià-Terrassa
- , Caleb Bastian
- & Yibin Kang
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Article
| Open AccessEpigenetic profiling for the molecular classification of metastatic brain tumors
The treatment of brain metastases is often limited by the ability to diagnose their origins. Here the authors generate DNA methylomes from the three most frequent types of brain metastases, identify epigenetic signatures specific to each type of metastasis and construct a DNA methylation-based classifier (BrainMETH) to advance brain metastasis diagnosis.
- Javier I. J. Orozco
- , Theo A. Knijnenburg
- & Diego M. Marzese
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Article
| Open AccessLévy-like movement patterns of metastatic cancer cells revealed in microfabricated systems and implicated in vivo
- Sabil Huda
- , Bettina Weigelin
- & Bartosz A. Grzybowski
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Article
| Open AccessRedox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen
Aerotaxis, chemotaxis towards oxygen, occurs in bacteria and likely in cancer cells. Here the authors find that confined cells from different tissues escape hypoxia by aerotaxis, a process independent of mitochondria and the HIF pathway, and dependent on EGF receptor interpretation of a ROS gradient in mammary cells.
- Mathieu Deygas
- , Rudy Gadet
- & Ivan Mikaelian
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Article
| Open AccessLNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment
Mechanism of lymph node (LN) metastasis induced by tumor associated macrophages (TAMs) remains unclear. Here they demonstrate that a long noncoding RNA LNMAT1 promotes LN metastasis of bladder cancer via recruitment of TAMs through epigenetic regulation of CCL2 expression.
- Changhao Chen
- , Wang He
- & Tianxin Lin
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Article
| Open AccessMacrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate metastatic colonization
Tumor microenvironment varies between primary and metastatic sites. Here they report tumor-associated macrophages from metastatic sites to be predominantly M2 type, and secrete IL-35 to promote metastasis through activation of JAK2–STAT6–GATA3 signaling.
- Chih-Chan Lee
- , Jiunn-Chang Lin
- & Muh-Hwa Yang
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Article
| Open AccessA small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer
Improved therapeutics are needed for treating breast cancer. Here they show the druggability of myoferlin with a small molecule inhibitor in breast cancer and demonstrate its anti-breast cancer effects in vitro and in vivo.
- Tao Zhang
- , Jingjie Li
- & Mingyao Liu
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Article
| Open AccessA reliable murine model of bone metastasis by injecting cancer cells through caudal arteries
Reliably modelling bone metastasis in mice is essential for research. Here, the authors present a new murine model for cancer metastasis based on intra-caudal artery injection that reliably recapitulates bone metastasis.
- Takahiro Kuchimaru
- , Naoya Kataoka
- & Shinae Kizaka-Kondoh
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Article
| Open AccessMacrophages are exploited from an innate wound healing response to facilitate cancer metastasis
The relationship between wound healing and cancer is intricate and complex. Here, the authors show that in breast cancer models an IL-6 driven co-expression of FAP and HO-1 in tumour-associated macrophages, similar to the wound healing response, facilitates migration and metastatic spread.
- Tamara Muliaditan
- , Jonathan Caron
- & James N. Arnold
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Article
| Open AccessFABP4 as a key determinant of metastatic potential of ovarian cancer
In ovarian cancer, metastatic phenotype may impact surgical outcomes. Here, the authors show miR-409-3p regulates FABP4 which can increase metastatic potential of ovarian cancer, and treatment with DOPC nanoliposomes containing either miR-409--3p mimic or FABP4 siRNA inhibits tumor progression in mice.
- Kshipra M. Gharpure
- , Sunila Pradeep
- & Anil K. Sood
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Article
| Open Accessp38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis
Polycomb group protein EZH2 is overexpressed in ER- breast cancer, promoting metastasis. Here, the authors show that independent of the polycomb group, phosphorylation of EZH2 at T367 by p38 promotes cytoplasmic localization of EZH2, binding to vinculin and other regulators of cell migration and invasion.
- Talha Anwar
- , Caroline Arellano-Garcia
- & Celina G. Kleer
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Article
| Open AccessTMEM106B drives lung cancer metastasis by inducing TFEB-dependent lysosome synthesis and secretion of cathepsins
One of the major causes of cancer-related mortality is represented by metastatic lung cancer. Here the authors characterize the role of TMEM106B in driving metastatic lung adenocarcinoma and suggest that TMEM106B-mediated secretion of cathespin impacts cell migration and invasion of lung cancer cells, increasing metastatic spreading.
- Samrat T. Kundu
- , Caitlin L. Grzeskowiak
- & Don L. Gibbons
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Article
| Open AccessReactive astrocytic S1P3 signaling modulates the blood–tumor barrier in brain metastases
When brain metastases form, the blood–brain barrier morphs into the blood–tumor barrier (BTB), surrounded by neuroinflammatory response. Here, the authors show that S1P3 is upregulated in neuroinflammatory response in highly BTB permeable lesions, and modulation of S1P3 could impact BTB permeability.
- Brunilde Gril
- , Anurag N. Paranjape
- & Patricia S. Steeg
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Article
| Open AccessmiR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity
Tumours produce soluble factors that contribute to the expansion of Gr-1+CD11b+ immature myeloid cells with TGFβ dependent immune suppressive function. Here, the authors show miR-130a and miR-145 target TβRII and reprogram these cells by altering the cytokine microenvironment, improving anti-tumour immunity and inhibiting metastasis in preclinical mouse models.
- Hiroki Ishii
- , Suman K. Vodnala
- & Li Yang
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Article
| Open AccessTargeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic transcriptional program
Histone modifications in cancer can contribute to pathogenesis. Here, the authors demonstrate that targeting epigenetic modifier Ezh2 hinders metastatic behaviour in Luminal B breast cancer models, and highlight a mechanism where Ezh2 contributes to metastatic behaviour by repression of FOXC1.
- Alison Hirukawa
- , Harvey W. Smith
- & William J. Muller
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Article
| Open AccessQuantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis
Tumour metastasis is dependent on tumour cell motility. Here, the authors investigate genes required for tumour cell motility by establishing a quantitative in vivo screening platform based on intravital imaging of human cancer metastasis in ex ovo avian embryos.
- Konstantin Stoletov
- , Lian Willetts
- & John D. Lewis
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Article
| Open AccessTAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis
Therapeutic options for triple-negative breast cancer (TNBC) metastasis are limited. Here they show nanoparticle-mediated delivery of TAK1 inhibitor 5Z-7-Oxozeaenol to inhibit TNBC lung metastasis in mice, and that TAK1 might promote TNBC cell adaptation in lung microenvironment by positive feedback mediated by P38 signaling.
- Oihana Iriondo
- , Yarong Liu
- & Min Yu
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Article
| Open AccessIntegrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis
The oligometastasis hypothesis suggests certain metastases are limited in extent and curable with focal therapies. Here they identify three integrated molecular subtypes of colorectal cancer liver metastasis, which complement clinical risk stratification to distinguish the subset of oligometastatic patients.
- Sean P. Pitroda
- , Nikolai N. Khodarev
- & Ralph R. Weichselbaum
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Article
| Open AccessA cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors
Cancer vaccines represent a promising personalized therapeutic approach to treating cancer. Here, the authors report the efficacy in a metastatic model of a cancer vaccine-mediated postoperative immunotherapy, based on the coencapsulation of the JQ1 and a photosensitizer ICG together with inactivated tumor cells into a hydrogel matrix.
- Tingting Wang
- , Dangge Wang
- & Yaping Li
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Article
| Open AccessACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity
The atypical chemokine receptor ACKR2 regulates immune responses. Here the authors confirm that ACKR2 depletion promotes primary tumor growth but show it has an anti-metastatic effect in mouse models of breast cancer by affecting myeloid differentiation and unleashing the anti-metastatic activity of neutrophils.
- Matteo Massara
- , Ornella Bonavita
- & Raffaella Bonecchi
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Article
| Open AccessDynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma
Biomarkers of the tipping point before metastasis in hepatocellular carcinoma (HCC) could help stratify patient treatment. Here, the authors study dynamic network biomarkers to identify CALM3 as a potential suppressor of metastasis, the level of which can predict overall survival and relapse-free survival in postoperative HCC.
- Biwei Yang
- , Meiyi Li
- & Jinglin Xia
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Article
| Open AccessA-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression
In melanoma, reduced ADAR1 impairs A-to-I microRNA editing. Here, the authors show that miR-378a-3p undergoes this editing in non-metastatic cells and the edited form of miR-378a-3p binds to the PARVA oncogene, inhibiting its expression and preventing melanoma progression and metastasis.
- Guermarie Velazquez-Torres
- , Einav Shoshan
- & Menashe Bar-Eli
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Article
| Open Access∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling
Aberrant expression of the Δ133p53 isoform is linked to many cancers. Here, the authors utilise a model of the Δ133p53 isoform that is prone to tumours and inflammation, showing that Δ133p53 promotes tumour cell invasion by activation of the JAK-STAT and RhoA-ROCK pathways in an IL-6 dependent manner.
- Hamish Campbell
- , Nicholas Fleming
- & Antony W. Braithwaite
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Article
| Open AccessMacrophages orchestrate breast cancer early dissemination and metastasis
Early dissemination of cancer cells has been reported to occur in certain breast cancer models. Here the authors show that intra-epithelial macrophages in the early pre-cancer lesions drive early cancer cell dissemination through Wnt-1 secretion and that such events impact the later development of metastasis.
- Nina Linde
- , Maria Casanova-Acebes
- & Julio A. Aguirre-Ghiso
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Article
| Open AccessMetas-Chip precisely identifies presence of micrometastasis in live biopsy samples by label free approach
Detecting metastatic cells in tumor/lymph node samples of breast cancer patients is extremely important for diagnosis. Here the authors develop a microelectronic biochip that detect the presence of invasive/metastatic cells in unprocessed biopsies and performs better than the current gold standards.
- Mohammad Saeid Nikshoar
- , Mohammad Ali Khayamian
- & Mohammad Abdolahad
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Article
| Open AccessBreast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7
The activation of TGF-β signaling has been implicated in cancer metastasis. Here, the authors show that OTUD1 suppresses metastasis by antagonizing the TGF-β pathway via the deubiquitination of SMAD7, and its loss correlates with poor prognosis in breast cancer.
- Zhengkui Zhang
- , Yao Fan
- & Long Zhang
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Article
| Open AccessThe low affinity neurotrophin receptor CD271 regulates phenotype switching in melanoma
The aggressive nature of melanoma cells relies on their ability to switch from a high-proliferative/low-invasive to a low-proliferative/high-invasive state; however, the mechanisms governing this switch are unclear. Here, using in vivo models of human melanoma, the authors show that CD271 is a key regulator of phenotype switching and metastasis formation.
- Gaetana Restivo
- , Johanna Diener
- & Lukas Sommer
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Article
| Open Access3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry
Extracellular matrix plays a central role in driving cancer development. Here the authors using an in vitro approach show that confining collagen architectures induce fast and persistent cell migration and the formation of multicellular network structures linked to vascular mimicry observed in tumours from patients.
- D. O. Velez
- , B. Tsui
- & S. I. Fraley
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Article
| Open AccessThe IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis
NF-κB regulates inflammation, cell survival, proliferation, and metastasis and is often hyperactivated in triple-negative breast cancer. Here the authors show that Morgana, a protein highly expressed in triple-negative breast cancers, drives NF-kB activation to promote metastasis and neutrophil recruitment.
- Federica Fusella
- , Laura Seclì
- & Mara Brancaccio
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Article
| Open AccessmiR-1199-5p and Zeb1 function in a double-negative feedback loop potentially coordinating EMT and tumour metastasis
miRNAs have been involved in tumour development and progression. Here the authors uncover a double feedback loop between miR-1199-5p and the Zeb1, potentially coordinating a protein involved in epithelial mesenchymal transition and tumour metastasis.
- Maren Diepenbruck
- , Stefanie Tiede
- & Gerhard Christofori
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Article
| Open AccessCancer-specific PERK signaling drives invasion and metastasis through CREB3L1
PERK stress signaling is an important driver of cancer invasion and metastasis, but chemical inhibitors of PERK cause side effects. Here, the authors find that CREB3L1 is required for PERK's pro-metastatic function in breast cancer, and its inhibition suppresses cancer invasion and metastasis.
- Yu-Xiong Feng
- , Dexter X. Jin
- & Piyush B. Gupta
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Article
| Open AccessThe cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells
High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.
- Amy E. Baek
- , Yen-Rei A. Yu
- & Erik R. Nelson
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Article
| Open AccessMolecular characterization of breast cancer CTCs associated with brain metastasis
Characterization of CTCs derived from breast cancer patients with brain metastasis (BCBM) may allow for early diagnosis of brain metastasis and/or help for treatment choice and its efficacy. In this study, the authors identify a unique signature, based on patient-derived CTCs transcriptomes, for BCBM- CTCs that is different from primary tumors.
- Debasish Boral
- , Monika Vishnoi
- & Dario Marchetti
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Article
| Open AccessSynergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration
Tumor cell proliferation and migration, key drivers of metastasis, can be mechanistically coupled in matrix embedded human sarcoma and carcinoma cells through cell density via a synergistic, paracrine signaling mechanism between Interleukins 6/8. Inhibition of this mechanism significantly decreases metastasis in mouse xenograft models.
- Hasini Jayatilaka
- , Pranay Tyle
- & Denis Wirtz
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Article
| Open AccessSenescent tumor cells lead the collective invasion in thyroid cancer
The senescence-associated secretory phenotype of stromal cells can promote tumorigenesis. Here, the authors show that senescent cancer cells are localized at the invasive front in human papillary thyroid carcinoma, and that senescent cancer cells drive collective invasion via CXCL12 in mouse models.
- Young Hwa Kim
- , Yong Won Choi
- & Tae Jun Park
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Article
| Open AccessLPP is a Src substrate required for invadopodia formation and efficient breast cancer lung metastasis
Lipoma preferred partner (LPP) mediates TGFβ-induced breast cancer cell migration and invasion. Here the authors show that LPP is a Src-family kinase substrate that regulates the formation of protrusions of the plasma membrane -called invadopodia- required for breast cancer metastasis.
- Elaine Ngan
- , Konstantin Stoletov
- & Peter M. Siegel